Study On Relationship Between HMGB1and Drug Resistance Of Pancreatic Cancer

Objective To study the influence of the expression of HMGB1to drug resistance of pancreatic cancer cells.Methods (1) Four human pancreatic cancer cell lines were treated with different concentrations and experiment durations of Gemcitabine. Real Time PCR and Western Blot were applied to measure the mRNA and protein of HMGB1before and after treatment with Gemcitabine respectively, then the relationships among them were analysed.(2) Two kinds of vectors-pSIREN-HMGB1/siRNA and pBABE-HMGB1were constructed. The former contains the siRNA sequence which targets the endogenous HMGB1gene, and the latter has subclone sequence of human HMGB1gene. The vectors were transfected into the pancreatic cancer cell lines with retrovirus and the stable clones were established with puromycin. The HMGB1expression was detected by Western blot and Real Time PCR. MTT evaluated IC50value to detect the sensitivity to Gemcitabine.Results The HMGB1is differently expressed in all the four pancreatic cancer cell lines. The expression of HMGBl is enhanced with the increasing concentration and the extending treating time of Gemcitabine. Silencing the expression of HMGB1decreased the viability of pancreatic cancer cells. The IC50of Gemcitabine increased while the expression of HMGB1was up-regulated.Conclusion HMGB1takes part in drug resistance of pancreatic cancer, and the down-regulation of HMGB1promotes Gemcitabine sensitivity of pancreatic cancer.