Latent Kaposi's sarcoma-associated herpesvirus infection in bladder cancer cells promotes drug resistance by reducing reactive oxygen species.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the major etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Recent studies have indicated that KSHV can be detected at high frequency in patient-derived bladder cancer tissue and might be associated with the pathogenesis of bladder cancer. Bladder cancer is the second most common cancer of the genitourinary tract, and it has a high rate of recurrence. Because drug resistance is closely related to chemotherapy failure and cancer recurrence, we investigated whether KSHV infection is associated with drug resistance of bladder cancer cells. Some KSHV-infected bladder cancer cell lines showed resistance to an anti-cancer drug, cisplatin, possibly as a result of down-regulation of reactive oxygen species. Additionally, drug resistance acquired from KSHV infection could partly be overcome by HDAC1 inhibitors. Taken together, the data suggest the possible role of KSHV in chemo-resistant bladder cancer, and indicate the therapeutic potential of HDAC1 inhibitors in drug-resistant bladder cancers associated with KSHV infection.