Advances in the exploration of adjuvant therapy of colon cancer with Chinese medicine

Yu-Xin Wei, Bing-Lin Shi, Huai-Yuan Zheng, An Yan, Xue-Hai Wei, Shi-Bo Zhao,2*, Zi-Hui Liu

1College of clinical, Youjiang Medical University for Nationalities, Baise 533000, China.2General Surgery, First People's Hospital of Fangchenggang, Fangchenggang 538000, China.3College of Nursing, Youjiang Medical University for Nationalities, Baise 533000, China.4College of Clinical Medicine, Guilin Medical University, Guilin 541000, China.5Hematology, First People's Hospital of Fangchenggang, Fangchenggang 538000, China.

Abstract Colon cancer is currently a highly prevalent cancer with a high mortality rate worldwide.Modern medical technology provides a range of treatments for colon cancer through different means, and research on the modulating adjuvant treatment of colon cancer with Chinese medicine is currently undergoing continuous theoretical and practical exploration to find highly effective herbal remedies to modulate, alleviate or treat the disease.The present study reviews different aspects of colon cancer in relation to different factors and the modulating adjuvant treatment of colon cancer with Chinese medicine.

Keywords: Chinese medicine; gene; adjuvant therapy; review

Highlight

This article examines and analyzes colon cancer from the perspective of traditional medicine complementing modern medicine in the treatment of colon cancer, with the aim of seeking more effective herbal modulation, alleviation or treatment of the disease.This study reviews different aspects of the correlation between colon cancer and different factors, as well as the modulating adjuvant treatment of colon cancer with Chinese medicine.

Colon cancer is a disease with a high morbidity and mortality rates around the world, endangering the physical and mental health of all humans.Only by fully understanding the pathogenesis of colon cancer can the disease be addressed at its source and the right medicine be prescribed.We are constantly exploring the close link between cancer and genes to uncover the mysteries.We are exploring the mechanism of Chinese medicine and adopting Chinese medicine treatment methods to regulate the body while playing a complementary role in treatment.Chinese medicine has fewer side effects compared to radiotherapy and chemotherapy for cancer, and can better save patients from some mental and physical torture and harm.

Correlation between colon cancer and genes

Association between colon cancer and ARHGAP17

ARHGAP17 (also known as RICH1) is one of the small G proteins among the regulatory proteins.

It is one of the regulatory proteins that are members of the small G protein family.The small G proteins can be classified as part of the nucleotide-dependent small GTP-binding proteins, whose major members include the Rho (RhoB, RhoA and RhoE) Rac, andCdc42subfamilies [1–3].The mechanism of action of ARHGAP17 in the cell body has not been systematically confirmed.However, it is now possible to confirm that it has been demonstrated that ARHGAP17 is involved in the maintenance of tight junctions by regulatingCdc42activity through binding to tight junction-associated proteins [4].Firstly, we elaborate the implications of the presence of different expression of ARHGAP17 in colon cancer and the condition and prognosis of the disease.The relationship between colon cancer and ARHGAP17 is continuously being explored.

Association of colon cancer with forkhead box protein (FOX) A1

Forkhead box protein (FOX) A1 is a member of the FOX family, and this gene is closely related to the growth and development of the organism and its pathological changes.TheNotchsignaling pathway plays an important role in the development of cancer cells and is responsible for regulating cell proliferation and differentiation [5–7].TheNotchsignaling pathway in cancer cells, especially in colon cancer, may lead to the growth and metastatic spread of malignant tumors because it is highly expressed and extremely active and excited [8, 9].In colon cancer cells, when FOX A1 expression is aberrantly increased, silencing its expression can be achieved by inhibiting the expression of phosphatase and tensin homolog (PTEN)/protein kinase (PK) deleted on chromosome ten.PTEN/protein kinase B (Akt) signaling pathway inhibits proliferation, colony formation, invasion and migration of cancer cells.It has been shown that the inhibitory effect of FOX A1 on the proliferation, invasion and metastatic spread of colon cancer cells is responsible for the silencing of the gene and is inextricably linked to the inhibition of theNotchsignaling pathway in its expression, and thatNotchactivation reversesNotchactivation reverses the tumor suppression by FOX A1 expression silencing [10].

Relevance of colon cancer to miRNA-34a

miRNA-34a is one of the miRNAs that have a variety of important functions, mainly in the body of biological cells regarding cell cycle changes, influencing cell migration function and cell aging cycle.In the treatment of tumors, the reactivation of miRNA-34a can block infiltration and metastasis of tumor cell process [11].However, abnormal expression of miRNA-34a may occur during the process of RNA expression, for example, abnormal expression of miRNA-34a will produce different RNAs and translate different functional proteins, and abnormal protein expression will lead to functional changes, and often this abnormal protein will lead to a series of changes in the cell, which may lead to functional changes or even lesions in the cell tissue.Luo et al [12].found that RNA can enhance the wnt/β-catenin signaling pathway by binding to miRNA-34a and sirt1, thus accelerating the progress of clinical treatment of colon cancer, and miRNA-34a has important implications in the clinical diagnosis of colon cancer.To explore some variability in the expression of miRNA-34a in benign and malignant cells, a study used a conventional real-time polymerase chain reaction method to extract total RNA and detect miRNA-34a expression [13].In a study of the mechanism by which theXIST/miRNA-34a signaling axis regulates the sensitivity of colorectal cancer cells to SW480 radiotherapy, Fu et al [14].explored and found that there was a significant upregulation increase in the expression ofXISTin tissue cells of colon cancer, and that downregulation ofXISTexpression increased the sensitivity of colon cancer to specific cellular radiation.The effect can be reversed by inhibiting the expression of miRNA-34a.miRNA-34a can be used to medicate the proliferation and metastasis of colon cancer cells by down-regulating specific genes in its expression, thereby causing apoptosis of the cancer cells [15].

Relevance of colon cancer to intestinal flora

Under normal physiological conditions, many microorganisms are involved in homeostasis, metabolism, excretion and bioimmune antagonism in the human body [16, 17].The microflora of the intestinal tract can inactivate carcinogens, but the high consumption of low-fiber, high-fat and high-energy foods in humans largely weakens the intestinal mucosal barrier and disrupts the internal environment, leading to dysbiosis and an increased incidence of colon cancer [18, 19].It has been found that activation of macrophages can promote epithelial mesenchymal transition, which is a very important process in the development and metastasis of colon cancer [20, 21].Therefore, dysbiosis of intestinal flora may stimulate epithelial mesenchymal transition of tumor cells, thus promoting the invasion and metastasis of colon cancer.Studies of the microbiota in tumor and normal intestinal tissues revealed higher levels of E.coli and Clostridium perfringens in colon cancer tissues than in normal intestinal tissues, and lower numbers of Lactobacillus and Bifidobacterium than in normal intestinal tissues [22, 23].E.coli directly causes DNA damage to intestinal epithelial cells, leading to the development of colon cancer [24].

Monotherapy conditioning for colon cancer

Ba Ji Tian's effect on colon cancer

Ba Ji Tian (Radix Morindae officinalis) is one of the traditional Chinese medicines, its medicinal effect has the advantages of dispelling wind and removing dampness, tonifying liver and benefiting kidney, and for human bones.Ba Ji Tian is also a food herbal medicine.Research on the pharmacological effects of Ba Ji Tian stated that it was first derived from the alcoholic extract of the drug to have an inhibitory effect on tumor cells.The study claimed that the alcoholic extract of Bacopa monniera mainly inhibits the formation of tumor cells by inhibiting the activity of the key protease phosphatidylinositol-3-activated alcoholin, which can eventually prevent the development of tumor cells from spreading.The alcoholic extract of Bacopa monniera contains a cyclic enol ether glycoside, whose monomeric portion includes osteotriol A, crystalloid and citronelloside, which have anti-tumor activity and significantly inhibit the activity of AP-1, a key protein activator in the induction of tumor cell development [25, 26].One of the main factors in the development of colon cancer lesions is the deterioration of the environment due to a constant inflammatory state of the intestine, with the development of inflammation and infection.It has been shown that dextran sulfate (DSS) induced ulcerative colitis in mice can inhibit the secretion of pro-inflammatory factors in the intestine and improve inflammation under the effect of alcoholic extracts of Bacopa monniera, leaving the barrier repair of the intestine intact and free from inflammatory damage [27, 28].By inhibiting the activation ofHIF-1αand COX-2/PGE2 signaling pathways, which in turn induces macrophage polarization towards M1-type macrophages, Bacopa monniera exerts an inhibitory effect on tumor angiogenesis, thereby influencing the process of colon cancer transplantation tumor development [29].

Effect of Pulsatilla on colon cancer

Pulsatilla chinensis (Bunge) Regel is a traditional Chinese medicine with the effects of clearing heat and detoxifying the blood, cooling the blood, drying dampness and stopping dysentery.It is cold in nature, bitter in taste and enters the stomach and large intestine meridians.Inflammation of the intestinal tract is an important factor in the development of colon cancer, and pulsatilla is effective in the treatment of ulcerative colitis [30].Pharmacological studies have shown that a good pharmacological component that can be extracted from B.alba is total saponin, which has excellent tumor inhibition, and B.alba can also play an antagonistic role in the body against bacteria and inflammation, maintaining the physiological balance of the body and enhancing the body's autoimmunity [31].It has been shown that the total saponin of P.alba in the human organism has an excellent inhibitory effect on the proliferation of human HT29 colon cancer cells, but also induces cancer cells to enter the apoptotic program, and it was found in experiments that the total saponin of P.alba in the human body on liver cancer H22 plays a good tumor suppression effect.The total saponin of Baicalein can also inhibit the proliferation of HT29 colon cancer cells through dose-dependent, which further establishes that it has a good regulatory effect on colon cancer, and the pharmacological effects on colon cancer need to be continuously studied and developed [32–34].

Effect of Scutellaria baicalensis on colon cancer

Scutellaria baicalensis Georgi belongs to the lung, gall bladder, spleen, large intestine and small intestine meridians, and its herbal therapeutic effects are mainly to clear heat and dry dampness, and to remove fire and detoxify toxins.A flavonoid extracted from the dried roots of Scutellaria baicalensis or obtained by other isolation techniques is baicalin [35].Research experiments have shown that baicalin has promising therapeutic modulation of cancer, with high biological activity and low toxic reactions and side effects [36].Baicalin can directly induce apoptosis, inhibit the secretion of inflammatory factors, suppress the proliferation and metastasis of cancer cells, and have powerful antioxidant effects.Baicalin can inhibit the development of HCT-116 cancer cells, allowing the cells to enter the apoptotic stage, and some studies suggest that this may be caused by the regulation of the expression of important factors in the body, such as Caspase-3 and Survivin.Baicalin inhibits PI3K phosphorylation, AKT activity and NF-κB nuclear translocation in the body, thus inhibiting the secretion of TNF-α, IL-6 and other inflammatory factors in the body, thereby reducing the inflammatory response of HT-29 cells, improving the inflammatory environment of the intestine, relieving discomfort, and giving full play to the anti-inflammatory effects of baicalin [37, 38].Baicalin can interfere with protein expression during the development of cancer cells, and the expression of cancer cells is down-regulated.Inhibition ofc-Mycexpression can indirectly induce apoptosis of colon cancer cells [39].In the process of proliferation and metastasis of cancer cells, baicalin inhibited the proliferation and metastatic invasion of human colon cancer SW480 cells in the organism, and the study showed that this mechanism may be inextricably linked to the down-regulation of COX-2 and MMP-9 protein expression [40].Baicalin, by virtue of its good antioxidant capacity, could upregulate DEPP expression and activate its downstreamRas/Raf/MEK/ERK and p16INK4A/Rbpathways, accelerating the senescence process of colon cancer cells [41].

Effect of Comfrey on colon cancer

Comfrey (Arnebiae Radix) is the dried root of the soft comfrey, hard comfrey or yellow-flowered soft comfrey of the family Comfreyaceae [42].It is often used clinically for the treatment of burns and some diseases due to its Chinese medicinal effects of clearing heat and detoxifying the blood, penetrating the rash and invigorating the blood, with good healing results [43].The herb contains a variety of chemical components, all with different effects and activities.Contemporary medical experiments and pharmacological experiments have discovered that Comfrey can effectively inhibit and destroy tumor cells, and when extracted, the different chemical components of Comfrey can be applied to different cancer cells to produce different degrees of cytotoxic activity, and its application in tumors has been continuously broadened [44–48].Comfrey has a group of active naphthoquinones with good medicinal properties, namely comfreyin, which not only enhances immunity but also produces effective utilization in the body for antiviral and anti-inflammatory purposes [49–51].With continuous research, it was found that comfreyin could achieve anti-tumor effects by inducing apoptosis as well as cell autophagy [52–54].The phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has a regulatory role in these key steps of cell proliferation migration and apoptosis [55, 56].

Treatment of colon cancer with Chinese herbal medicine

Effects of Chinese herbal formulas for strengthening the spleen and benefiting the qi on colon cancer–taking Si Jun Zi Tang as an example

The formula of Si Jun Zi Tang is described inTaiping Huimin Heji Jufangas a combination of ginseng (Ginseng Radix et Rhizoma), atractylodis Macrocephalae Rhizoma, poria and roasted licorice (Glycyrrhizae Radix et Rhizoma).In this formula, ginseng, which is a great tonic for vital energy, is the ruling herb; Atractylodes, which dries up dampness and resolves turbidity, is the subject herb; Poria, which helps to drain dampness and strengthen the spleen, is the adjuvant herb; Glycyrrhizae, which clears heat and detoxifies the body, is the ambassador herb.In addition, Si Jun Zi Tang is often used in the adjuvant treatment of cancer because of its anti-tumor, anti-fatigue, inflammatory and related gastrointestinal disorders [57].According to research, Si Jun Zi Tang has an important effect on the human immune system, promoting the secretion of cellular immune factors IL-2, CD4+ and CD8+ by lymphocytes and increasing immunoglobulins IgG, IgA and IgM, which have the function of promoting the recovery of immune organs in the body in cancer treated with chemotherapy [58].By improving the immune function of the intestinal mucosa in the body, the immune system is better coordinated and cooperated.The predisposing factors for colon cancer may be thought to be related to the disruption of the homeostasis of the intestinal flora and an unbalanced pathological environment in the intestine is inextricably linked to the consequences of colon cancer [59].Si Jun Zi Tang is quite effective in treating Qi deficiency in the spleen and stomach, maintaining the balance of flora in the intestinal tract in a normal physiological homeostatic environment; It can also act as a potentiator for the clinical chemotherapeutic drug fluorouracil (5-FU) to better inhibit the development of colon cancer cells [60].

Effects of qi tonifying and conciliating herbal formulas on colon cancer-taking the example of Ban Xia Di Xuan Xin Tang

According to theTreatise on Typhoid, the formula is composed of Banxia (Pinelliae Rhizoma), Scutellaria baicalensis Georgi, Zingiberis Rhizoma, Huang Lian (Coptidis Rhizoma), Ginseng Radix et Rhizoma, Ziziphi Spinosae Semen and Glycyrrhizae Radix et Rhizoma (roasted licorice), with the effect of clearing heat and dispersing lumps.It is used clinically for treating acute and chronic gastroenteritis, chronic colitis, chronic hepatitis and early cirrhosis of the liver, with weak middle energy and mixed cold and heat.In recent years, it has been found that this formula is also effective in the treatment of colon cancer.This formula helps to support positive Qi and regulate the Qi flow, which can inhibit the proliferation and migration of colon cancer cells and induce apoptosis in the body [61].In combination with the chemotherapeutic agent fluorouracil (5-FU), this formula can lower the expression level of mTOR protein in the body, which in turn can upregulate the expression level of the oncogenePTENprotein, thus preventing the proliferation and metastasis of colon cancer HT-29 cells [62].This is because it can make tumor cells down-regulate VEGFR2 mRNA expression, thus inhibiting tumor autocrine or paracrine VEGF secretion, and tumor cells enter apoptosis [63, 64].Experimental studies have shown that Ban Xia Di Xuan Xin Tang can improve the immune microenvironment in the human intestine, regulate the level of cellular immune factors secreted by lymphocytes, improve the inflammatory environment, repair mucosal damage, maintain the physiological balance of intestinal flora and reduce the development of carcinogenic factors [65].

Effect of astringent Chinese herbal formulas on colon cancer-taking Si Shen Wan as an example

According to theStandard Rules for the Treatment of Disease, Si Shen Wan is composed of Psoraleae Fructus, Myristicae Semen, Schisandrae Chinensis Fructus, Evodiae Fructus, Zingiberis Rhizoma, and jujube (Ziziphi Spinosae Semen).The formula is made up of Evodiae Fructus, Zingiberis Rhizoma and Ziziphi Spinosae Semen, herbs that warm the spleen and earth, nutmeg, which astringently stops diarrhea, Evodiae Fructus, herb which warms the spleen and stomach, and Wu Wei Zi, which strengthens the kidneys and astringents, and Ziziphi Spinosae Semen, which nourishes the spleen and stomach.Studies have found that Si Shen Wan has the effects of warming the kidneys and dispersing cold, astringent to the intestines and stopping diarrhea, anti-inflammatory and antiseptic, anti-tumor, and regulating immune function [66].It has been shown that Si Shen Wan is effective in ulcerative colitis, inhibiting inflammation in the body and has immunomodulatory effects on the intestinal mucosa [67].It regulates the balance of flora in the intestine, keeps the intestine from being in a poor inflammatory environment, and is good at preventing the development of colon cancer.CD133 is a tumor marker for colon cancer, and its abnormal expression indicates an increased risk of cancer.The mechanism of CD133 expression can be regulated and normalized by Si Shen Wan, which needs to be further explored [68].

Conclusion

This article has described the correlation between multiple factors and colon cancer, and provided an in-depth analysis of colon cancer in terms of Chinese medicine treatment and the current practical application of Chinese medicine.Colon cancer endangers human health worldwide and requires a constant search for the best treatment options.With the rapid development of current experimental research, TCM is also expanding its research in the direction of regulating the treatment of colon cancer.TCM conditioning treatment of colon cancer is not only limited to the above description, but there are also herbal medicines that clear heat and detoxify the body, invigorate blood circulation and remove blood stasis, and have anti-mutagenic effects for cancer treatment.Chinese herbal conditioning not only has medicinal value, but also improves diet, complications, recurrence and metastasis and drug resistance, reduces adverse drug reactions and alleviates patients' pain.At this stage, the research on the treatment of colon cancer with Chinese medicine is not deep enough, the research on the mechanism is still at the basic stage, and the research on the biological activity is insufficient.There is a need for continuous exploration through multidisciplinary cross-collaboration and clinical trials to open up the landscape of Chinese medicine for colon cancer and better improve the means of treating cancer [69].

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