Effect of p16(INK4a) on chemosensitivity in nasopharyngeal carcinoma cells

The p16(INK4a) tumor suppressor gene is frequently inactivated in nasophary ngeal carcinoma (NPC) and hence it may play an important role in the suppre ssion of this tumor. In order to study the effect of p16(INK4a) restoration in NPC cells, full-length human p16(INK4a) gene was transfected into a NPC cell line, CNE1. Four individual clones with differential levels of p16(IN K4a) protein expression, were selected for further studies. The introductio n of p16(INK4a) into CNE1 cells induced growth suppression through G(0)/G(1 ) cell cycle arrest; however, the cell growth rate was not correlated to th e levels of p16(INK4a) protein expression. To study whether transfection of p16(INK4a) could protect NPC cells from radiation, cisplatin and 5-fluorou racil (5FU), the cellular sensitivity of p16(INK4a) transfectants and vecto r control were investigated. An increase in sensitivity to 5FU was observed (2-fold compared to IC50) in all 4 clones compared to vector-transfected c ontrol. p16(INK4a) transfection also resulted in increased sensitivity to c isplatin (1.5-1.8-fold) in 3 out of 4 cell lines. However, no difference in radiosensitivity was found between the p16(INK4a) transfectants and the co ntrol. These findings indicate that p16(INK4a) suppresses NPC cell growth t hrough G(0)/G(1) arrest and modulating cellular response to chemotherapeuti c drugs in NPC cells. Therefore, restoration of p16(INK4a) may have a thera peutic purpose in the treatment of NPC.