| Objective:A retrospective clinical study was conducted to investigate the effects of salvia combined with FOLFOX6 chemotherapy on postoperative gastric cancer,providing animal studies to further investigate the mechanism of action of cryptotanshinone(CPT)against gastric cancer.Methods:The study was comprised of two parts: Clinical observation and experimental study.1.Clinical observation component: Sixty-two patients who underwent surgery for gastric cancer and completed postoperative adjuvant chemotherapy at the First Affiliated Hospital of Anhui University of Chinese Medicine from January 1st,2018,to December 31 st,2019,were observed and followed up.Patients were divided into treatment and control groups according to whether or not Danshin injection was used during chemotherapy,and the tumor marker profile,three-year survival rate and survival time,progression-free survival time(PFS)of disease,and occurrence of toxic side effects after chemotherapy were observed before and after chemotherapy in both groups.The Kaplan-Meier method in survival analysis was used to estimate the three-year survival time and disease-free survival time,and the Log-Rank test was used to compare the survival rates.2.Experimental study component: The tumors were transplanted into the stomach wall of nude mice after subcutaneous tumor formation using 5-FU-resistant SGC-7901 gastric cancer cells,and treated with no treatment,saline,cryptotanshinone,5-fluorouracil(5-FU)and CPT+5-FU for 6 weeks.The pathological morphology of the tumors was observed under microscope after HE staining.q RT-PCR and WB assay were performed to detect whether cryptotanshinone could inhibit the growth and proliferation of gastric cancer and reverse 5-fluorouracil resistance by inhibiting JAK2/STAT3 signaling pathway.Results:1.Clinical observation result: In terms of tumor markers,after three cycles of treatment,the tumor markers in both groups decreased(<0.05),and the values of CEA and CA199 decreased significantly in the treatment group compared with the control group(<0.05),but the values of CA125 and CA724 in the treatment group were not statistically significantly different compared with the control group(>0.05);in terms of survival time,the three-year survival rate was 62.5% in the control group and 70.0% in the treatment group,and there was no statistical difference between the two groups(>0.05).In terms of survival time,the three-year survival rate was 62.5% in the control group and 70.0% in the treatment group,with no statistical difference between the two groups(>0.05),but the median PFS time was 7.50 months in the control group and8.78 months in the treatment group,which was statistically significant(<0.05).The incidence of bone marrow suppression,liver function abnormalities and gastrointestinal reactions was lower in the treatment group than in the control group,which was statistically significant(<0.05),but there was no statistically significant difference between the two groups in skin mucosal reactions and neurotoxic reactions(>0.05).2.Experimental study result: The average tumor mass in the control group was2.28 g,and the tumor suppression rate was only 6.74%,while the average tumor mass in the cryptotanshinone group was 0.58 g,and the tumor suppression rate was only76.29%,and the average tumor mass in the CPT+5-FU group was 0.47 g,and the tumor suppression rate was only 80.93%,with statistically significant differences(<0.05).p-JAK2,STAT3,Bcl-2,Bcl-XL,Mcl-1 and survivin m RNA levels were lower and Bax m RNA was higher in the CPT group compared with the control group.p-JAK2,p-STAT3,Bcl-2,Bcl-XL,Mcl-1 and survivin protein expression levels were lower and Bax protein expression levels were higher in the CPT group compared with the control group,and the difference was statistically significant(< The CPT+5-FU group had lower levels of MDR1 and lower levels of P-gp expression than the 5-FU group,with statistically significant differences(<0.05).the CPT+5-FU group had lower levels of JAK2,STAT3,Bcl-2,Bcl-XL,Mcl-1 and survivin m RNA than the 5-FU group,and higher levels of Bax m RNA than the 5-FU group;p-JAK2,p-STAT3,Bcl-2,Bcl-XL,Mcl-1 and survivin protein expression levels were lower and Bax protein expression levels were higher in the CPT+5-FU group compared with the 5-FU group,with statistically significant differences(<0.05).Conclusion:1.Salvia injection accelerates the decrease of CEA and CA199 during chemotherapy in postoperative patients with gastric cancer;2.Salvia injection prolongs the duration of PFS in postoperative patients with gastric cancer;3.Salvia injection can reduce the adverse effects of chemotherapy in patients;4.CPT can inhibit the growth and proliferation of gastric cancer by inhibiting the JAK2/STAT3 signaling pathway;5.CPT can enhance the effect of 5-FU chemotherapy by inhibiting the JAK2/STAT3 signaling pathway and reducing the expression of P-gp,thus reversing 5-FU drug resistance. |
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