Vol. 8, Issue 3 (2019)

Author(s):
Mohammad Enamul Hoque

Abstract:
Effective management of colorectal cancers is often limited by their relative decreasing of response to chemotherapy, partly due to development of resistance against the chemotherapeutic agents or severe side effects of the drugs. To overcome these barriers, multiple drug therapy is a common approach in cancer treatment. We selected two drugs cisplatin and tunicamycin, with unique mode of cytotoxicity, to establish effective dose combinations optimizing the synergism and thus reducing the drug induced side effects. Eight different solutions of cisplatin ranging from 0 µg/ml to 16 µg/ml were evaluated in combination with eight different solutions of tunicamycin ranging from 0ng/ml to 800ng/ml by in vitro chemosensitivity assay against two colorectal cancer cell lines HCT116WT and HCT116P53N, where the later lacks the tumours suppressing gene, TP53. The result showed significant difference in chemosensitivity between the two cell lines towards the experimental solutions, where HCT116P53WT was found more susceptible. The IC50 for cisplatin and tunicamycin alone against HCT116WT were found 2.5 µg/ml and 50 ng/ml respectively. The dose combinations of cisplatin to tunicamycin that induce synergism against HCT116WT include 0.25 µg/ml: 25 ng/ml; 0.5 µg/ml: 25 ng/ml; 1 µg/ml: 25 ng/ml and 1 µg/ml: 12.5 ng/ml. The dose combinations for the same against HCT116P53N were revealed markedly high as 2 µg/ml: 25 ng/ml; 2 µg/ml: 50 ng/ml; 4 µg/ml: 12.5 ng/ml and 4 µg/ml: 25 ng/ml, indicating P53 induced cytotoxicity in HCT116WT significantly. To conclude, these findings can serve as strong evidence for p53 role & combination chemotherapy as an effective strategy in cancer treatment with reduced risk of side effects and resistance development.