Down-regulation of p110β expression increases chemosensitivity of colon cancer cell lines to oxaliplatin.

Abstract

This study examined the synergetic effect of class IA Phosphoinositide 3-kinases catalytic subunit p110β knockdown in conjunction with oxaliplatin treatment on colon cancer cells. Down-regulation of p110β by siRNA interference and oxaliplatin treatment were applied in colon cancer cell lines HT29, SW620 and HCT116. MTT assay was used to measure the inhibitory effect of p110β knockdown on the proliferation of colon cancer cell lines. SubG1 assay and Annexin-V FITC/PI double-labeling cytometry were applied to detect cell apoptosis. And cell cycle was evaluated by using PI staining and flow cytometry. The expression of caspase 3, cleaved PARP, p-Akt, T-Akt and p110β was determined by western blotting. The results suggested that down-regulation of p110β expression by siRNA obviously reduced cell number via accumulation in G(0)-G(1) phase of the cell cycle in the absence of notablely increased apoptosis in colon cancer cell lines HT29 and SW620 (S phase arrest in HCT116). Moreover, inhibition of p110β expression increased oxaliplatin-induced cell apoptosis and cell cycle arrest in HT29, HCT116 and SW620 cell lines. In addition, increases of cleaved caspase-3 and cleaved PARP induced by oxaliplatin treatment were determined by immunoblotting in p110β knockdown group compared with normal control group and wild-type group. It is concluded that down-regulated expression of p110β could inhibit colon cancer cells proliferation and result in increased chemosensitivity of colorectal cancer cells to oxaliplatin through augmentation of oxaliplatin-induced cell apoptosis and cell cycle arrest.

• Authors: Weicheng Liu, Guihua Wang, Xiaonian Cao, Xuelai Luo, Zhaoming Li, Yu Deng, Xiaolan Li, Shijia Wang, Mengfei Liu, Junbo Hu, Jing Wang
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 32 Issue 2 Pg. 280-286 (Apr 2012) ISSN: 1672-0733 [Print] China
• PMID: 22528234 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Oxaliplatin
• Phosphatidylinositol 3-Kinases
• Class I Phosphatidylinositol 3-Kinases
• PIK3CB protein, human

Topics

• Antineoplastic Agents (administration & dosage)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Class I Phosphatidylinositol 3-Kinases
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Dose-Response Relationship, Drug
• Down-Regulation
• Drug Synergism
• Humans
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Phosphatidylinositol 3-Kinases (metabolism)