Low-dose fractionated radiation potentiates the effect of cisplatin independent of the hyper-radiation sensitivity phenomenon in human lung cancer cell lines

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Introduction: Previous studies have shown that low dose fractionated radiation (LDFR) potentiates the effect of various chemotherapeutic drugs such as taxol, taxotere, gemcitabine etc. in tumor cell lines that harbor hyper-radiation sensitivity (HRS) phenomenon. The purpose of the present study was to investigate the effects of cisplatin in combination with LDFR in human lung cancer cell lines with or without HRS. Methods: Two human lung cancer cell lines, UKY-29 and H-157 were exposed to X-rays (0.1-6 Gy) to determine the presence of HRS by colony forming assay. Further, effects of cisplatin either alone or in combination with LDFR (4X0.5 Gy) (cisplatin added immediately before irradiation) on cell survival and apoptosis were studied in these cell lines by colony forming and TUNEL (fluorescence microscopy) assays respectively. Results: H-157 cells were more radiosensitive than UKY-29 cells (SF₂ = 0.18; D₀ = 109 cGy vs. SF₂ = 0.37; D₀ =120 cGy). HRS phenomenon was present in H-157 but was absent in UKY-29 cells. Further, the H-157 cells were more sensitive to cisplatin treatment as compared to UKY-29 cells (IC₅₀ = 0.04 μg/mL vs. 0.25 μg/mL). A combination of IC₅₀ concentration of cisplatin with LDFR resulted in 1-5 fold increase in chemo-enhancement ratio (CER) for clonogenic inhibition (CER for UKY-29 = 6.5; H-57 = 4.8) when compared with cisplatin plus 2 Gy treatment (CER for UKY-29 = 1.4; H-157 = 3.7). Similarly, a 2-3 fold increase in CER for apoptosis was observed with combined treatment of cells with LDFR plus cisplatin (CER for UKY-29 = 6.2; H-157 = 11.1) when compared to 2 Gy plus cisplatin (CER for UKY-29 = 1.2; H-157 = 6.5). Conclusion: The present results show that low-dose fractionated radiation can chemopotentiate cisplatin toxicity in human lung cancer cell lines irrespective of HRS status. Further studies to elucidate the molecular mechanisms of chemopotentiation of cisplatin by LDFR are in progress. (This work was supported by Kentucky Lung Cancer Research Program).