Mechanism for natural resistance of melanoma cells against anti-tubulin drugs

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: Yasuhira Shinji 岩手医科大学, 医学部, 助教 (90311729)
• Co-Investigator(Kenkyū-buntansha): AKASAKA Toshihide 岩手医科大学, 医学部, 教授 (30137525) ; SUGIYAMA Toru 岩手医科大学, 医学部, 教授 (40162903) ; MAESAWA Chihaya 岩手医科大学, 医学部, 教授 (10326647)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 遺伝子病理診断学 / 細胞分裂 / 悪性黒色腫 / 分裂攪乱 / アポトーシス / 分裂期崩壊

Outline of Final Research Achievements

We made an attempt to elucidate mechanisms for common natural resistance of melanoma against paclitaxel by studying relationship between acute apoptosis and loss of clonogenicity after the drug treatment. Propensities to apoptosis of several melenoma cell lines were strongly correlated with expression of anti-apoptotic proteins, and forced down-regulation of them remarkably increased occurrence of apoptosis. Low propensity to apoptosis, however, did not necessarily lead to an increased colony-forming ability. Most of these apoptosis-resistant cells underwent either abnormal division or mitotic slippage and eventually lost clonogenicity after paclitaxel treatment. Slipped cells often showed apoptosis-like morphology, while they did not show any signs of mitochondrial outer membrane permeabilization and showed only weak degree of caspase activation. Our results suggest that reluctance to apoptosis is unlikely to be a main cause for paclitaxel resistance.

Free Research Field

分子生物学