Synergistic Combinatorial effect of L-asparaginase and Trastuzumab against HER2+ breast cancer cells

Abstract

Multi-targeted drug combinations which selectively inhibit the proliferation of cancer cells are required for effective anticancer treatment. The current anti-HER2 positive breast cancer therapy involves Trastuzumab and doxorubicin drug combination which produces toxic side effects in clinical settings including high cardiotoxicity. In this study, anticancer activity of single drug as well as the drug combination effect of L-asparaginase (Celginase) and Trastuzumab (Herceptin) was studied on HER2 positive breast cancer (SKBR3) cells. Inhibition of cell proliferation assay based on fluorescence readout was studied to estimate the anticancer effect of the drugs. HUVEC cells were used as negative control cells. Individually as a single drug, Trastuzumab (Herceptin) and L-asparaginase (Celginase) showed anticancer activity against SKBR3 cells with IC50 value of 0.031ng/ml and 1.168µg/ml respectively. The drug combination interaction of Trastuzumab and L-asparaginase resulted in combination index of less than 1(CI < 1) showing their synergistic effect against SKBR3 cells. No cytotoxic effect was observed in control HUVEC cells. The results suggested that the antitumor activity of Trastuzumab and L-asparaginase against HER2 positive breast cancer was found specific to HER2 positive cancer (SKBR3) cells. This synergistic drug interaction of L-asparaginase and Trastuzumab could be further explored to as an alternative to current drug combination therapy against the HER2 positive breast cancer.