Bmi1 inhibition enhances the sensitivity of pancreatic cancer cells to gemcitabine

نویسندگان

  • Tao Yin
  • Zhengle Zhang
  • Bin Cao
  • Qingke Duan
  • Pengfei Shi
  • Hengqiang Zhao
  • Soriba Naby Camara
  • Qiang Shen
  • Chunyou Wang
چکیده

As the standard therapy for pancreatic cancer, gemcitabine shows limited efficacy in pancreatic cancer patients because of chemoresistance. Aberrant expression of Bmi1 has been reported to activate multiple growth-regulatory pathways and confer anti-apoptotic abilities to many cancer cells. However, the role of Bmi1 in response of pancreatic cancer cells towards gemcitabine resistance remains elusive. In this study, we found that certain dose of gemcitabine treatment induced Bmi1 expression in pancreatic cancer cells. Knockdown of Bmi1 enhanced ROS production and promoted the cytotoxic effect of gemcitabine. The increased oxidative stress upon gemcitabine treatment could disrupt mitochondrial membrane and decrease mitochondrial membrane potential, eventually leading to apoptosis. Bmi1 inhibition also suppressed the activation of NF-κB signaling and the expressions of downstream molecules in pancreatic cancer cells treated with gemcitabine. Moreover, we observed Bmi1 inhibition sensitized the pancreatic xenograft tumors to gemcitabine in vivo. Taken together, our study demonstrated that Bmi1 could decrease the sensitivity of pancreatic cancer cells to gemcitabine through increasing oxidative stress and inhibiting NF-κB signaling, thus Bmi1 may serve as a promising target for sensitizing pancreatic cancer cells to chemotherapy.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Bmi1 Enhances Tumorigenicity and Cancer Stem Cell Function in Pancreatic Adenocarcinoma

BACKGROUND Bmi1 is an integral component of the Polycomb Repressive Complex 1 (PRC1) and is involved in the pathogenesis of multiple cancers. It also plays a key role in the functioning of endogenous stem cells and cancer stem cells. Previous work implicated a role for cancer stem cells in the pathogenesis of pancreatic cancer. We hypothesized that Bmi1 plays an integral role in enhancing pancr...

متن کامل

YAP Inhibition by Resveratrol via Activation of AMPK Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine

Resveratrol, a natural polyphenol present in most plants, inhibits the growth of numerous cancers both in vitro and in vivo. Aberrant expression of YAP has been reported to activate multiple growth-regulatory pathways and confer anti-apoptotic abilities to many cancer cells. However, the role of resveratrol in YES-activated protein (YAP) expression and that of YAP in pancreatic cancer cells' re...

متن کامل

Double inhibition of NF-κB and XIAP via RNAi enhances the sensitivity of pancreatic cancer cells to gemcitabine.

The majority of patients with pancreatic cancer are resistant to gemcitabine. One of the mechanisms involved is the anti-apoptotic ability of these cells. The median lethal dose (LD50) of gemcitabine for PANC-1 cells was higher than that for Mia PaCa-2 cells and the former had higher nuclear factor-κB (NF-κB) and X-linked inhibitor of apoptosis pr...

متن کامل

Inhibition of AKT2 Enhances Sensitivity to Gemcitabine via Regulating PUMA and NF-κB Signaling Pathway in Human Pancreatic Ductal Adenocarcinoma

Invasion, metastasis and resistance to conventional chemotherapeutic agents are obstacles to successful treatment of pancreatic cancer, and a better understanding of the molecular basis of this malignancy may lead to improved therapeutics. In the present study, we investigated whether AKT2 silencing sensitized pancreatic cancer L3.6pl, BxPC-3, PANC-1 and MIAPaCa-2 cells to gemcitabine via regul...

متن کامل

Secreted APP promotes pancreatic cancer cell survival

Background: Amyloid Precursor Protein (APP) and ADAM10, main α-secretase involved in generation of secreted APP (sAPPα), are overexpressed in pancreatic cancer. Results: Inhibition of APP processing by ADMA10 prevents anchorage independent growth and survival of cancer cells. Conclusion: Inhibition of sAPPα generation enhances chemotherapeutic potential of gemcitabine. Significance: Supplementi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016