RB protein status and chemosensitivity in non-small cell lung cancers.

Abstract

The retinoblastoma gene product (RB protein), one of the tumor suppressor proteins has been found as wild-type in most non-small cell lung cancer (NSCLC) cells, usually showing multidrug chemoresistance. Recently, carboplatin (CBDCA) and etoposide (VP-16) have been introduced for the treatment of NSCLC as well as small cell lung cancer (SCLC). We examined the correlation of RB protein expression levels and chemosensitivities of a panel of NSCLC cell lines with wild-type RB for CBDCA and VP-16 in order to clarify the role of RB protein in chemoresistance of NSCLC cells. There was significant correlation between chemosensitivity and high level of RB protein expression (P=0.049 for VP-16, P=0.016 for CBDCA). We next examined the effect of VP-16 on RB protein status and cell cycle phases of two NSCLC cell lines (Ma-12, the most chemosensitive cell line; Ma-31, the most chemoresistant cell line). VP-16 suppressed RB protein expression level of Ma-12 cells but did not suppress that of Ma-31 cells, following 24 h exposure at 0.1-10 microM. And the alteration of phosphorylation status of Rb protein expression were quite different in these cells. After the treatment of VP-16, dephosphorylated RB protein became dominant in Ma-12 cells, but phosphorylated RB protein became dominant in Ma-31. High sensitive non-small lung cancer Ma-12 cells were accumulated in G2/M phases of the cell cycle. But no major changes were found in low sensitive non-small lung cancer Ma-31 cells. This shows that phosphorylation status of RB protein might be useful for the assessment for the sensitivity to VP-16 and for the cell cycle inhibition.