Effect Of Cisplatin Combined With Rapamycin On Proliferation Of Endometrial Cancer Cells At Different Sugar Concentrations

Background: Obesity,diabetes,delayed menopause,premature menarche,and high estrogen levels are the main causes of endometrial cancer.Among them,obesity is most closely related to endometrial cancer,and it is also associated with poor prognosis in patients with endometrial cancer.The greater the patient's body mass index,the greater the chance of endometrial cancer.Factors such as pharmacokinetic changes caused by abnormal glucose metabolism and metabolic disorders in the body reduce the chemotherapy efficacy of patients with endometrial cancer.Using endometrial cancer cells to investigate the changes of cell proliferation,apoptosis and cycle and the changes of major signaling pathways in patients with abnormal endometrial cancer with glucose metabolism,and observe the mTOR inhibitor rapamycin monotherapy under different sugar concentrations.Combined with the inhibitory effect of cisplatin on tumors,the molecular biological mechanism of the above interventions was clarified.Exploring the feasibility of targeted intervention combined with chemotherapy to improve the therapeutic efficacy of patients with endometrial cancer with abnormal glucose metabolism.Methods: The endometrial cancer cell lines HEC-1B and Ishikawa were cultured in vitro,and the cells were cultured in a high glucose concentration medium for 24 hours.The old medium was discarded and replaced with different sugar concentrations(low sugar group: 11 mmol/L,high sugar group: The cells were treated with 25 mmol/L of DMEM in complete culture.The effects of cisplatin,rapamycin and their combination on the proliferation of endometrial cancer cells were observed by CCK-8 method.PI staining and Annexin V/PI method were used.The effects of cisplatin,rapamycin and their combination on the cycle and apoptosis of endometrial cancer cells were detected by two concentrations of glucose.Western blotting was used to detect the endometrial cancer cells under different sugar concentrations.Expression of AKT/mTOR/S6 signaling pathway-associated proteins(p-AKT,p-S6,t-AKT,t-S6),apoptotic proteins(MCL-1),and cyclin D1 are clearly defined in different Signal transduction pathways for cellular metabolism in a metabolic environment.Results: The endometrial cancer cell lines Ishikawa and HEC-1B were cultured under different sugar concentrations,and the proliferation of two endometrial cancer cells was found to be dose-dependent.The higher the drug concentration was,the higher the drug concentration was inhibited by cisplatin or rapamycin alone.The higher the rate,the synergistic inhibition of tumor cells in combination with the two drugs,the lower cell inhibition rate at high glucose concentration,and the sensitivity of endometrial cancer cells to drugs;the higher the drug concentration in single drug,the early cell The higher the apoptotic rate,the synergistic effect of the two drugs on the promotion of tumor cell apoptosis,the low glucose concentration will enhance the sensitivity of the cells to drugs;the endometrial cancer cells are mainly blocked in G2 phase when cisplatin alone,Rapa The main block of the G1 phase of tumor cells,combined with the use of two drugs,inhibits the proliferation of Ishikawa and HEC-1B cells by blocking the S phase.The cells are more sensitive to drugs at low glucose concentrations;Western blotting results show In Ishikawa and HEC-1B cells,the expression levels of t-AKT,p-AKT,t-s6,p-S6,MCL-1 and cyclin D1 were decreased when the two drugs were used alone or in combination,and the low glucose concentration was observed.Lower endometrial cancer Cellular strong cisplatin and rapamycin-sensitive.These results demonstrate that abnormal glucose metabolism promotes proliferation of endometrial cancer cells by modulating Akt/mTOR/S6 signaling pathway,and has significant anti-tumor effects when combined with cisplatin and rapamycin.Conclusion: The combination of mTOR inhibitor rapamycin and cisplatin has synergistic anti-tumor effect on endometrial cancer.Abnormal changes in the PI3K/Akt/mTOR signaling pathway not only promote the development of endometrial cancer with abnormal glucose metabolism,but also may be an important molecular mechanism for chemoresistance in such patients.Targeted intervention in the above signaling pathways,combined with the use of chemotherapy drugs,It will produce a synergistic effect and improve the therapeutic effect,and is expected to become a new breakthrough point in the treatment of abnormal endometrial cancer with abnormal glucose metabolism.