Experimental Study On The Efficacy And Mechanism Of Zhongqi Kangai Decoction Combined With S-1 In The Treatment Of Advanced Gastric Cance

Purpose:The stomach is one of the important organs for the human body to receive,digest and absorb food with its function included in the functions of the“Pi Wei”in Traditional Chinese Medicine(TCM);some functions belong to the category of“Zhong Qi”in TCM.For patients with gastric cancer,the tumor growing in the stomach,surgical resection of gastric tissue and the toxic side effects of chemotherapy can cause or aggravate the damage of“Qi”in the stomach,hence rebuilding“Zhong Qi”is the primary objective of TCM treatment of gastric cancer..On the other hand,integrated TCM and Western medicine treatment of gastric cancer,two drugs chemotherapy regime,TCM treatment utilizes the“Protective”treatment model,minimizing the harm to the human body caused by the side effects of chemotherapy;for single-drug chemotherapy,TCM utilizes the“Jia Zai”treatment model of strengthening,protecting the body(“Fu Zheng”)and destorying the tumor(“Qu Xie”),to increase the effect of tumor treatment while reducing the toxic and side effects of chemotherapy.In this study,the oral chemotherapeutic drug Tegafur,which has been widely used in clinical practice,was combined with the Chong Jian Zhong Qi Anti-Cancer Formula(Formula 2)with dual equal emphasis on“Fu Zheng”and“Qu Xie”in the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,and the Reduce-dose Chong Jian Zhong Qi Anti-Cancer Formula(Formula 1),which halved the dosage of“Qu Xie”components,to intervene in nude mice with human gastric cancer sgc-7901 transplanted tumors,to clarify the differences in the effects and side effects of the two prescriptions in treating tumors,as well as the mechanism of tumor treatment.Material and method:To establish a subcutaneous tumour model in orthotopic nude mice,the human gastric cancer cell SGC-7901 suspension was subcutaneously inoculated into the right axilla of the nude mice.After successful modeling,the nude mice were divided into 4 groups using the random number table method:1.Model control Group;2.Tegafur Group;3.Formula 1combined with Tegafur(Combine 1)Group;4.Formula 2 combined with Tegafur(Combine2)Group.Component TCM herb of Formula 2 are::Tai Zi Shen、Fu Ling、Chao Bai Zhu、Chen Pi、Jaing Ban Xia、Sha Ren、Zhi Gan Cao、Yi Yi Ren、Tu Fu Ling、Ban Zhi Lian、Bai Hua She She Cao、E Shu、Zhe Bei Mu。The Model Control Group was given oral administration of normal saline,0.3ml per mouse,once a day,for 15 consecutive days;the Tegafur Group was given oral administration 0.1ml of Tegafur and 0.2ml of normal saline,once a day,for 15 consecutive days;according to commonly used experiments The Effect-dose Relationship calculated from the body surface area ratio of animals and humans,the Combine 1 Group was given oral administration of 0.f2ml o Formula 1 at concentration of 403mg/kg,Tegafur 0.1ml,once a day,for 15 consecutive days;Combine 2 Group was given oral administration of 0.2ml of Formula 2 at concentration of 481mg/kg,Tegafur 0.1ml,once a day,for 15 consecutive days.Tumor volume was measured once every 3 days for 15 consecutive days.At the end of the experiment,after 18 hours of fasting,the nude mice were euthanized by cervical dislocation,with each group’s data collected separately.The experiment indicators collected include the weight of nude mice before and after medicine administration,the weight of the tumor,using an electronic scale and the tumor inhibition rate was then calculated.Tumor volume was calculated using the measured data.Western blot was used to determine the effects of tumor suppressor gene APC protein,receptor tyrosine kinase Erb B protein,mucin MUC2 and silent information regulator SIRT1 protein in tumour cells.SPSS26 statistical software was used to analyze the data obtained from the experiment,and P<0.05was considered statistically significant.Results:1.General state of nude mice after gavageThe general state of the nude mice in each group was that after 10 days of intragastric administration,the nude mice showed obvious emaciation,listlessness,decreased activity times,dull skin color and reduced diet.2.Changes in body weight of nude mice before and after administrationThe body weights of nude mice in each group before administration were:Model Control Group 20.2±0.916g;Tegafur Group 20.033±0.7116g;Combine 1 Group 1 20.172±0.898g;Combine 2 Group 20.143±0.974g.After 15 days of drug administration,the weights of nude mice in each group were:Model Control Group 18.6±1.437g,Tegafur Group 14.357±1.334g,Combine 1 Group15.414±1.557g and Combine 2 Group 2 17.017±1.329g.Changes in body weight of nude mice after treatment:the body weight of nude mice in Combine 2 Group was significantly higher than that of Combine 1 Group and Tegafur Group(P<0.05),and the weight of Model Control Group was significantly heavier than that of Tegafur Group and Combine 1 group(P<0.05).The body weight of the Combine 2 Group and the Model Control Group was similar.The body weight of the nude mice in each group decreased significantly(P<0.05)compared with the body weight after administration.3.Changes of tumour volume in nude mice before and after administrationAfter drug intervention,the tumour volume of nude mice in each group gradually increased.From the 6th day,the tumour volume in each group was:Model Control Group315.304±30.146mm~3,Tegafur Group 282.576±27.198mm~3,Combine 1 Group276.845±20.681mm~3,Combine 2 Group 247.567±20.992mm~3.Compared with the Model Control Group,the tumour volume of the nude mice in the Combine 2 Group and the Combine 1 Group were smaller,with statistical significance(P<0.05).Compared with the Combine 2 Group group,the tumour volume of the Combine 1 Group group and the Tegafur group was smaller(P<0.05).After 15 days of drug intervention,the tumour volumes in each group were:Model Control Group 792.580±64.646mm~3,Tegafur Group 673.503±60.366mm~3,Combine 1 Group 652.095±56.474mm~3,Combine 2 Group 479.430±33.677mm~3.Compared with the Model Control Group,the tumour volume of the nude mice in the Combine 2 Group,Combine 1 Group and Tegafur group were smaller than that in the Model Control Group(P<0.05).Among them,the tumour volume in the Combine 2 Group compared with the Combine 1 Group and the Tegafur Group was also smaller than that in the Tegafur Group(P<0.05).4.Net body weight of nude mice after administrationAfter 15 days of drug intervention,the net body weights(net body weight=body weight-tumour weight)of nude mice in each group were Model Control Group 16.552±1.474g,Tegafur Group 12.542±1.396g,and Combine 1 Group 13.607±13.607g,Combine 2 Group15.434±1.364g.Compared with the Model Control Group,the net body weight of the Combine 1 Group and the Tegafur group were significantly reduced(P<0.05).The net body weight of the Combine 2 Group was significantly heavier than the Tegafur group and the Combine 1 Group(P<0.05).5.Tumour weight and tumour inhibition rate in nude mice after administrationAfter 15 days of drug intervention,the tumour weights of each group were Model Control Group 2.0483±0.224g,Tegafur Group 1.815±0.184g,Combine 1 Group 1.807±0.174g;Combine 2 Group 1.582±0.155g;compared with the Model Control Group,the tumour weights of the three groups were significantly lighter(P<0.05).The tumour weight of Combine 2 Group was the lightest,which was statistically significant compared with the Tegafur group and the Combine 1 Group(P<0.05).After drug intervention,the tumour inhibition rates of the 3 groups were respectively the Tegafur group(11.39%),the Combine 1Group(11.77%),and the Combine 2 Group(22.72%).6.Western blot resultsAfter the experiment,Western Blot was used to measure the expression of tumour suppressor gene APC protein,receptor tyrosine kinase Erb B protein,mucin MUC2 and silent information regulator SIRT1 protein in tumour cells of each group of nude mice.The expression of tumour suppressor gene APC protein Combine 2 Group was the highest,which was significant compared with the other 3 groups(P<0.05).This shows that the addition of full dose of“Qu Xie”TCM medicines in the Combine 2 Group can significantly increase the expression of APC proteins,which can better prevent genes that stimulate cell division from being turned on too frequently and prevent excessive cell growth,inhibiting gastric cancer tumour cells.The APC protein in the Model Control Group is the least,suggesting that without drug intervention,the APC protein in tumour cells would decrease rapidly.The expression of receptor tyrosine kinase Erb B protein Combine 2 Group was the lowest,compared to the other 3 groups(P<0.05).This suggests that the Combine 2 can effectively suppress Erb B protein in cells.Compared with the Model Control Group,the SIRT1 protein Combine 2 Group and the Tegafur Group had less SIRT1 protein(P<0.05).This indicated that Combine 2 could effectively suppress Erb B and SIRT1 protein in cells.The expression of mucin MUC2 in each group was not statistically significant.Conclusion:1.At the end of the experiment,the body weight of nude mice with gastric cancer in the 4groups was significantly reduced compared with that before gavage,and the reduction in the Tegafur Group was the most,indicating that tumor cells and gavage itself can cause functional damage to the digestive system,and the side effects of chemotherapy can make the damage worse.This is consistent with the clinical situation of“Zhong Qi”damage in patients with gastric cancer.2.After halving the dose of“Qu Xie”Chinese medicine in Combine 2 for gastric cancer-bearing nude mice,the body weight of the nude mice was significantly higher than that of Tegafur Group at the end of the experiment;full dosage of“Qu Xie”Chinese medicine retained the same protection effect.It shows that the combination of Chong Jian Zhong Qi Anti-Cancer Formula and Tegafur played a similar protective role.3.Tegafur has the effect of inhibiting the growth of gastric cancer tumor in nude mice,and this inhibitory effect is significantly increased after combined with Chong Jian Zhong Qi Anti-Cancer Formula,especially shown in the Combine 2 Group which emphasizes both“Fu Zheng”and“Qu Xie”.This demonstrates the Chong Jian Zhong Qi Anti-Cancer Formula combined with Tegafur shows the effect of the“Jia Zai”model.4.The inhibitory effect of Chong Jian Zhong Qi Anti-Cancer Formula combined with Tegafur on tumor growth in nude mice with gastric cancer may be achieved by up-regulating the expression of APC gene and down-regulating the overexpression of Erb B protein and SIRT1gene.5.Chong Jian Zhong Qi Anti-Cancer Formula emphasizes both“Fang Hu”and“Qu Xie”,can restore or partially restore the damaged“Zhong Qi”.When combined with Tegafur,based on protective and restorative effects,it can show“Jia Zai”model effects.