Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells

Pancreas. 2017 Oct;46(9):1173-1179. doi: 10.1097/MPA.0000000000000910.

Abstract

Objectives: Rab family members are key regulatory factors that function as molecular switches in multiple phases of vesicular trafficking. Our previous study demonstrated that Rab27A and Rab27B overexpression may predict a poor outcome of pancreatic ductal adenocarcinoma. The purpose of this study was to investigate the role of Rab27A and Rab27B in the progression of pancreatic cancer.

Methods: We down-regulated Rab27A and Rab27B expression in pancreatic cancer cell lines. The regulatory effects of knockdown Rab27A and Rab27B on pancreatic cancer cell were measured by cisplatin assay, invasion assay, proliferation assay, and Western blot assay.

Results: Rab27A and Rab27B down-regulation enhances sensitivity to cisplatin and induces apoptosis in ASPC-1 and PANC-1 cells. In addition, down-regulation of Rab27A reduced the invasive and proliferative ability of ASPC-1 cells, and Rab27B knockdown significantly prevented cancer invasion and proliferation in PANC-1 cells.

Conclusions: Our findings provide evidence that Rab27A and Rab27B play significant roles in cell invasion, proliferation, and apoptosis, as well as in chemotherapy resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cisplatin / pharmacology
  • Down-Regulation
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA Interference
  • rab GTP-Binding Proteins / genetics*
  • rab GTP-Binding Proteins / metabolism
  • rab27 GTP-Binding Proteins / genetics*
  • rab27 GTP-Binding Proteins / metabolism

Substances

  • Antineoplastic Agents
  • rab27 GTP-Binding Proteins
  • RAB27A protein, human
  • Rab27B protein, human
  • rab GTP-Binding Proteins
  • Cisplatin