Sensitization of TRAIL-resistant cervical cancer cells through combination of TRAIL and fucoxanthin treatments.

Abstract

Cervical cancer, the second most common cause of cancer death in women worldwide, is a malignant neoplasm arising from cells originating in the cervix uteri. Currently, surgery combined with chemo- and radiotherapy is the major therapeutic approach for women with early-stage cervical cancer. However, recurrent cervical cancers from acquired chemo-resistance remain a major cause of therapeutic failure. In this study, we assessed the effects of the combination of TRAIL with fucoxanthin, which has been reported to suppress the cervical cancer cells growth on the cervical cancer treatments. HeLa cells, SiHa cells, and CaSki cells were used as in vitro model. Mice xenograft was used as in vivo model. TRAIL-resistant cells were generated from CaSki cell line. The activity of PI3K/Akt pathway was detected by Western blot. Cell viability was measured by MTT assay. We observed TRAIL-resistant cervical cancer cells were more sensitive to fucoxanthin treatments. By establishing a TRAIL-resistant cell line from CaSki, we found the TRAIL-resistant cells showed upregulated PI3K/Akt pathway. Moreover, CaSki TRAIL-resistant cells were more sensitive to the combination of TRAIL with either Akt inhibitor or fucoxanthin than treatment with TRAIL or fucoxanthin alone. Our in vitro and in vivo xenograft experiments demonstrate that the combination of TRAIL with fucoxanthin showed synergistically inhibitory effects on cervical cancer cells. The findings of this study suggest that the combined use of fucoxanthin and TRAIL might be a useful strategy against TRAIL-resistant cervical cancer.