Effects of anti-heparanase monoclonal antibody in combination with paclitaxel on proliferation, migration and invasion of breast cancer cell lines / 肿瘤

ABSTRACT

Objective: To investigate the effects of anti-heparanase monoclonal antibody (anti-HPA mAb) in combination with paclitaxel (PTX) on proliferation, migration and invasion of breast cancer MCF-7, MCF-7/F5 and MDA-MB-231 cells. Methods: The expression levels of HPAmRNA in MCF-7, MCF-7/Fs and MDA-MB-231 cells after treatment with anti-HPA mAb were detected by reverse transcription-PCR (RT-PCR). The proliferation of the three breast cancer cell lines after treatment with different concentrations of anti-HPA mAb or PTX alone or in combination was detected by MTT assay. The cell cycle distribution and the abilities of migration and invasion of these breast cancer cells after different treatment modalities were examined by flow cytometry (FCM), wound healing assay and Transwell assay, respectively. Results: The expression levels of HPA mRNA in MCF-7/F5 and MDA-MB-231 cells after treatment with 10 and 20 nmol/L anti-HPA mAb were lower than those of murine immunoglobulin C (IgG) treatment group (all P < 0.05). The proliferation of MCF-7, MCF-7/F5 and MDA-MB-231 cells after treatment with anti-HPA mAb or PTX alone was inhibited in a concentration-dependent manner (all P < 0.05). The proliferative inhibition rates of the three breast cancer cell lines after treatment with combination of anti-HPA mAb and PTX were higher than those of any single drug treatment groups (all P < 0.05). The ratios of G0/G1 phase of the three breast cancer cell lines after treatment with combination of anti-HPA mAb and PTX were lower than those of the control groups (three breast cancer cell lines without any treatment), and the ratios of G2/M phase were opposite (P < 0.05, P < 0.01), with a typical sub-diploid peak which appeared before C0/G1 phase. The abilities of migration and invasion of MCF-7/F5 and MDA-MB-231 cells after treatment with combination of anti-HPA mAb and PTX were lower than those of the control, murine IgG and single drug treatment groups (all P < 0.05). Conclusion: Anti-HPA mAb in combination with PTX have synergistic inhibitory effect on the abilities of proliferation, migration and invasion of breast cancer cells, and this mechanism may be associated with the arrest in G2/M phase.