Abstract:

Objective    To evaluate the anti-proliferative effect and targeting ability of paclitaxeloctreotide conjugates on H446 small cell lung cancer (SCLC) cells. Methods    PTX-OCT, 2PTX-OCT， PTX-Tyr-OCT and 2PTX-Tyr-OCT were synthesized by coupling  cytotoxic paclixtel (PTX) to somatostatin analog octreotide (OCT).  mRNA expressions of human somatostatin receptor subtypes (SSTRs) were detected in H446 cells and fibroblasts by real-time PCR. The cytotoxicity of paclitaxel and the conjugates (at different treatment concentrations and periods) was determined by MTT assay. Cell cycle variation and apoptosis were analyzed by flow cytometry 24h after the treatment with 1000nmol/L of paclitaxel, PTX-OCT, 2PTX-OCT，PTX-Tyr-OCT and 2PTX-Tyr-OCT. Results    H446 cells expressed mRNA of the five SSTRs, while no SSTR mRNA expression was detected in fibroblasts. The conjugates had an anti-proliferative effect similar to paclitaxel, inhibiting the growth of H446 cells in a dose-(1-1000nmol/L) and time- (24h, 48h and72h) dependent manner. However, the cytotoxicity of the conjugates to fibroblasts was much lower than that of paclitaxel(P<0. 05). Flow cytometry results indicated that the conjugates blocked H446 cells at the G2/M phase. Conclusion     Paclitaxel-octreotide conjugates have significant prospects in targeted therapy mediated by SSTRs in human SCLC.

Key words: Small cell lung cancer; Paclitaxel-octreotide conjugates; Somatostatin receptor; Targeted