Evaluation of cisplatin treatment given concurrently with pulsed irradiation in cisplatin sensitive and resistant human ovarian carcinoma cell lines.
The aim was to investigate the effect of combined treatment of cisplatin with acute or pulsed radiation in human ovarian carcinoma cells sensitive and resistant to cisplatin. Human ovarian cancer cell parental line A2780s and a derivative cisplatin-resistant line A2780cp were given cisplatin treatment before a single acute dose irradiation or concurrently during a pulsed-dose irradiation sequence. Cells were irradiated in the confluent state, trypsinized and plated after treatment. When the combined treatment for cisplatin was given before acute irradiation, the results showed additive to superadditive effects for both cell lines. However, the superadditivity was only significant in the sensitive cell line. For the concomitant treatment of cisplatin during pulsed-dose irradiation the results were additive, except for the highest cisplatin dose in the A2780cp line where subadditivity was observed. The results indicate that the combined treatments could be clinically useful even though the results are mostly not superadditive. However, high-dose cisplatin (3 microg ml(-1)) caused a subadditive effect in the resistant cell lines for pulsed irradiation. Thus, high-dose cisplatin to overcome resistance is not effective. Cisplatin with both acute and pulsed irradiation showed additive effects indicating no advantage of using cisplatin in pulsed irradiation where sublethal damage repair may be greater.
Leblanc
J M
JM
ORCC, The Ottawa Hospital, ON, Canada.
Raaphorst
P
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; D002945:Cisplatin