FHIT protein enhances paclitaxel-induced apoptosis in lung cancer cells

✍ Scribed by Cheol Hyeon Kim; Jung Sun Yoo; Choon-Taek Lee; Young Whan Kim; Sung Koo Han; Young-Soo Shim; Chul-Gyu Yoo

• Book ID: 102269076
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 324 KB
• Volume: 118
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.21573

✦ Synopsis

Abstract

The fragile histidine triad (FHIT) gene is a frequent target of deletions in lung cancer. Previous studies have shown that FHIT gene transfer into lung cancer cells lacking FHIT expression results in induction of apoptosis. However, the effect of FHIT expression on apoptosis induced by chemotherapeutic agents and its intracellular mechanism is poorly understood. This study was undertaken to elucidate the effect of FHIT expression and the role of Bcl‐2‐caspase signaling in paclitaxel‐induced apoptosis in lung cancer cells. NCI‐H358 lung cancer cells, which lack FHIT expression, were stably transfected with plasmid vector containing FLAG‐tagged wildtype FHIT. We investigated effects of paclitaxel on apoptosis, activation of caspase system and expression of Bcl‐2 family. We next evaluated whether these effects were reversed by blocking FHIT expression using siRNA. Paclitaxel enhanced apoptosis in FHIT‐expressing cells compared to that in control vector‐transfected cells, and this enhancement was suppressed by siRNA treatment. Activities of caspase‐3 and caspase‐7, but not of caspase‐8, were higher in FHIT‐expressing cells than in control vector‐transfected cells, and this was reduced by siRNA treatment. When caspase activation was blocked by a pan‐caspase inhibitor in FHIT‐expressing cells, paclitaxel‐induced apoptotic cell death was decreased similar to that in control vector‐transfected cells. Bcl‐2 and Bcl‐xL expressions were down‐regulated after paclitaxel treatment in FHIT‐expressing cells, whereas Bax and Bad expressions were up‐regulated. These were reversed by siRNA treatment. These results indicate that paclitaxel‐induced apoptosis enhanced by FHIT expression in lung cancer cells might be associated with modulation of Bcl‐2‐caspase signaling. © 2005 Wiley‐Liss, Inc.