Study On The Effect Of MiR-34a On Drug Resistance Of Pancreatic Cancer By Regulating Stem Cells And Its Mechanism

Pancreatic cancer is a kind of malignant tumor with high mortality and poor prognosis.At present,postoperative adjuvant chemotherapy is still the main treatment for pancreatic cancer,but long-term chemotherapy will cause drug resistance of pancreatic cancer,so the treatment of drug resistance of pancreatic cancer is the problem we need to solve.Studies have shown that pancreatic cancer stem cells can produce various types of differentiated cells,which can regenerate the tumor and eventually lead to chemotherapy failure.Therefore,PCSC targeted therapy has become a promising treatment plan for multi drug resistance of pancreatic cancer.MiR-34 a,known as tumor suppressor,can regulate renal cancer,bladder cancer and other cancer stem cells,but the mechanism between miR-34 a and pancreatic cancer stem cells is not clear.Therefore,in this study,miR-34 a was taken as the target to explore whether miR-34 a can regulate the drug resistance of pancreatic cancer by regulating pancreatic cancer stem cells and its mechanism.MTT method and PCR method were used to detect the drug sensitivity of cells to gemcitabine and the content of miR-34 a,to explore the correlation between miR-34 a and resistance of pancreatic cancer;flow cytometry was used to detect the influence of miR-34 a on the proportion of pancreatic cancer stem cells,and stem cell spheroidization,cell invasion and migration experiments were used to detect its influence on stem cell dryness;Notch1 overexpression plasmid and PCR were constructed,Western blotting and other methods described the specific mechanism of miR-34 a regulating pancreatic cancer stem cells.Finally,the subcutaneous tumor model of nude mice was constructed and verified in vivo.The results showed that the content of miR-34 a was negatively correlated with the sensitivity of gemcitabine in pancreatic cancer cell lines;The high expression of miR-34 a increased the sensitivity of pancreatic cancer cells to gemcitabine and decreased the stem cell dryness;over expression of Notch 1 reversed the sensitization of miR-34 a to gemcitabine to some extent and further proved that miR-34 a played a regulatory role by directly combining with Notch 1 At the animal level,the results showed that increasing the expression level of miR-34 a enhanced the chemosensitivity of gemcitabine,and the over expression plasmid of Notch 1 inhibited the sensitization of miR-34 a.In vivo and in vitro,we have proved that miR-34 a can regulate pancreatic cancer stem cells and drug resistance by combining with Notch 1,which provides a theoretical basis for the clinical treatment of pancreatic cancer.