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Modulating activity of indomethacin to vincristine cytotoxicity in various human carcinoma cells.

The modulating activity of indomethacin to vincristine (VCR) was investigated in thirty human pulmonary carcinoma cell lines (adenocarcinoma 9, large cell carcinoma 9, squamous cell carcinoma 6, small cell carcinoma 6) and five other cell lines (colon carcinoma 2, melanoma 1, teratocarcinoma 1, thymoma 1). The survival of these cell lines treated with VCR with or without indomethacin (2 microg/ml) for 72 hours were examined using MTT assay, and IC50 values were calculated. When the cutoff level of potent combined effect in clinical use was set at 2-fold increase of sensitivity, the positive rate was 100% for adenocarcinomas and large cell carcinomas, 25% for squamous cell carcinomas, 33% for small cell carcinomas. Mean modulating index was 2.91 in adenocarcinomas, 1.92 in squamous cell carcinomas, 3.06 in large cell carcinomas and 1.67 in small cell carcinomas. Of the cell lines of other tumors, three cell lines (colon carcinoma 1, melanoma 1, teratocarcinoma 1) showed the potent combined effect of VCR and indomethacin, while indomethacin was not effective in modulating activity to VCR in a thymoma cell line and fibroblast cells. In conclusion, it is considered that modulating activity of indomethacin for VCR is a general effect for various human cancer cells, and combined use with VCR and indomethacin may be a useful modulation therapy for the advanced lung cancer.