Chemopotentiating effects of low-dose fractionated radiation on cisplatin and paclitaxel in cervix cancer cell lines and normal fibroblasts from patients with cervix cancer.

Abstract

The aim of the present study was to compare the effects (assessed by clonogenic survival and γH2AX foci assays) of low-dose fractionated radiation LDFR (4 × 0.125 Gy, 4 × 0.25 Gy and 4 × 0.5 Gy) versus single radiation doses (0.5 Gy, 1 Gy and 2 Gy) on cisplatin and paclitaxel in HRS-negative cervix cancer cell lines SiHa and CaSki to see if the effects of LDFR can emerge in cells that not present low-dose hyper-radiosensitivity (HRS) phenomenon. Additionally, we report the effects in normal fibroblasts (HRS-negative and HRS-positive) from two patients with cervix cancer to see if the chemopotentiating effects of LDFR also apply to normal cells. LDFR (4 × 0.125 Gy, 4 × 0.25 Gy and 4 × 0.5 Gy) as well as single doses (0.5 Gy, 1 Gy and 2 Gy) enhanced cytotoxicity of cisplatin and paclitaxel in all the cell lines. Cisplatin-potentiating effects were maximum with LDFR 4 × 0.5 Gy, and were two-fold greater than those with a single dose of 2 Gy in SiHa, CaSki and HFIB2 cells. Paclitaxel-enhancing effects were also maximum with LDFR 4 × 0.5 Gy, however only in HRS-positive HFIB2 fibroblasts were significantly greater than those with a single dose of 2 Gy. The results demonstrate that LDFR may enhance the effects of cisplatin and paclitaxel in SiHa and CaSki cells, although they lack HRS phenomenon, and show that the magnitude of the potentiating effects of LDFR depends on cytostatic type and the size of low doses. In normal fibroblasts the chemopotentiating effects of LDFR seem to depend on HRS status. In conclusion, the unique enhancing effects of LDFR on cisplatin in cervical cancer cell lines, even when HRS negative, suggest that all patients with cervical cancer may benefit from the addition of LDFR to adjuvant cisplatin-based chemotherapy.