Basic study on low power laser in cancer chemotherapy-Rebersal of cisplatin resistance-

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 06807130
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: UDAGAWA Yasuhiro School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (80118918)
• Co-Investigator(Kenkyū-buntansha): MIYAZAKI Toyohiko School of Medicine, Assistant, 医学部, 助手 (20174162)
• Project Period (FY): 1994 – 1995
• Keywords: Laser / Activi oxygen / Ovarian cell line / Cisplatin resistance / GST / GSH / Reversal of resistance

Research Abstract

First, the cytotoxic effect of laser irradiation was investigated. Cisplatin (CDDP) resistant cell lines we chose were RTSG and RMG-II,both of which were established from human ovarian cancer by ourselves. The mechanism of resistance is the increase of glutathione-S-transferase (GST) activity for RTSG and other resistance factor for RMG-II,YAGlaser was irradiated on cells at a wave length of 1060nm and output power of 60W.The survival rate decreased with elevation in the energy density. The growthes of RMG-II and RTSG were inhibited completely at 860J/cm^2 and at 1150 J/cm^2, respectively. Secondly, changes in glutathione (GSH) contents and GST activities of RTSG and RMG-II by laser irradiation were measured. RTSG lost GST activity remarkably by laser irradiation but no such chage was seen in GST of RMG-II.The contents of GSH in both cells were not changed following laser irradiation. Furthermore, we tried to evaluate the synergisitic effect of CDDP and laser irradiation on RTSG and RMG-II.It was shown that laser irradiation enhanced the CDDP cytotpxicity in both cell lines, and especially the cytotoxicity of CDDP on RTSG was enhanced significantly. However, it was suspected that the enhancement of the sensitivity of CDDP occured by not only laser irradiation but also heat resulting from laser irradiation. Then, we examined the thermal effect. As to the condition, the temperature of medium and duration of treatment were the same as those described for the experiment with laser irradiation. It waa shown that heat did not influence cell growth or the cytotoxicity of CDDP.Thus, it is considered that the enhancement of the CDDP sensitivity was not due to thermal effect, but to laser light itself. These data suggest that inactivation of GST by laser irradiation leads to decrease in CDDP-GSH conjugates, with enhancement of antitumor activity of CDDP.