Effects of Hydroxychloroquine Co-administered with Chemotherapeutic Agents on Malignant Glioma Cell Lines : in vitro Study

Abstract

Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines (U87MG, T98G) were treated with chemotherapeutic agents alone or with antimalaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-(4,5-dimethyl-2-thiazol-2 yl) 2,5-diphenyltetrazolium bromide (MTT) assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents(doxorubicin, vincrisitne, nimustine, and cisplatin), the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance(ANOVA) yielded a statistically significant two-sided p-value of 0.0033(doxorubicin), 0.0005(vincrisitne), 0.0007(nimustine), and 0.0003(cisplatin) on U87MG cell lines and 0.0006(doxorubicin), 0.0421(vincrisitne), 0.0317(nimustine), and 0.0001(cisplatin) on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.