Overexpression of peroxisome proliferator activator receptor γ (PPARγ) has been implicated in many types of
cancer including
cervical cancer.
Radiation therapy remains the main nonsurgical modality for the treatment of
cervical cancer. The present study reports the impact of pharmacological inhibition of PPARγ in enhancing the radiosensitization of
cervical cancer cells in vitro. Three
cervical cancer cell lines (HeLa, SiHa, and Me180) were treated with a PPARγ inhibitor,
T0070907, and/or radiation. The changes in
protein, cell cycle,
DNA content, apoptosis, and cell survival were analyzed. The PPARγ is differentially expressed in
cervical cancer cells with maximum expression in ME180 cells.
T0070907 has significantly decreased the
tubulin levels in a time-dependent manner in ME180 cells. The decrease in the
tubulin levels after
T0070907 in ME180 and SiHa cells was associated with significant increase in the cells at the G2/M phase. The changes in the
tubulin and G2/M phase were not evident in HeLa cells.
T0070907 reduced the
protein levels of PPARγ; however, PPARγ silencing had no effect on the α-
tubulin level in ME180 cells suggesting the PPARγ-dependent and -independent actions of
T0070907. To ascertain the impact of synergistic effect of
T0070907 and radiation, HeLa and ME180 cells were pretreated with
T0070907 and subjected to radiation (4 Gy).
Annexin V-
fluorescein isothiocyanate analysis revealed increased apoptosis in cells treated with radiation and
T0070907 when compared to control and individual treatment. In addition,
T0070907 pretreatment enhanced radiation-induced tetraploidization reinforcing the additive effect of
T0070907. Confocal analysis of
tubulin confirmed the onset of mitotic catastrophe in cells treated with
T0070907 and radiation. These results strongly suggest the
radiosensitizing effects of
T0070907 through G2/M arrest and mitotic catastrophe.