The Effect of Hyperthermia on Chemosensitivity of Renal Cell Carcinoma Cell Lines in vitro

Lee, Sang Lin; Lee, Eun Sik; Park, Won Hee

Abstract

PURPOSE: Cellular biology of response to hyperthermia was understood and localizing hyperthermic equipments were developed recently. It was known that hyperthermia suppressed renal cell carcinoma cell growth in vitro and increased the sensitivity of chemotherapeutic agents in malignant melanoma. We investigated the effect of hyperthermia on chemosensitivity of renal cell carcinoma cell lines in vitro. MATERIALS AND METHODS: Human renal cell carcinoma cell lines, Caki-1(negative multidrug-resistance) and A-498(positive multidrug-resistance) were used. Chemotherapeutic agent(cisplatin or adriamycin) was added to media with appropriate cell counts and hyperthermia(43oC) was applied in 2 and 4 hours duration. The cell growth was measured by MTT colorimetric assay and each experiment was repeated eight times. The effects of hyperthermia on chemosensitivity of renal cell carcinoma cell lines were compared using dose modification factor(DMF) of IC50 of chemotherapeutic agents. RESULTS: In 2-hour treatment at 43oC, the cell growth suppression of Caki-1 and A-498 were 15% and 16% respectively and in 4-hour treatment, the suppression percentage was increased to 36% and 46% respectively. In Caki-1 cell lines, DMFs of cisplatin treated groups in 2 and 4 hour hyperthermia were 0.9 and 0.8 respectively and DMFs of adriamycin treated groups were 0.9 and 0.9 respectively. There was no change of chemosensitivity in Caki-1. In A-498 cell lines, DMFs of cisplatin with 2 and 4 hour hyperthermia groups were 0.7 and 0.4 respectively and DMFs of adriamycin treated groups were 0.9 and 0.5 respectively. Thus, 4 hours hyperthermia increased the chemosensitivity in A-498 cell lines. CONCLUSIONS: These results suggest that hyperthermia increased the chemosensitivity of renal cell carcinoma cell lines in vitro but there was some difference in each cell line. It is necessary to investigate what the mechanism of increasing chemosensitivity is and what affects a difference of chemosensitivity in each cell line.