Previous studies demonstrate that volume-sensitive chloride currents are distinctly activated in cervical cancer cells, but not in human papillomavirus (HPV)-immortalized and normal cervical cells. The aim of this study is to investigate the regulation of cell volume in response to hypotonic stress in cervical cells with different tumor potential. The effects of Cl- and K+ channel blockers in the process of regulatory volume decrease (RVD) was also studied. The results showed that cervical cancer cells were able to respond to either 250 mOsm/kg or 200 mOsm/kg hypotonic stress well. HPV-immortalized cells readjusted cell volume well in 250 mOsm/kg hypotonicity, but were not able to mediate RVD in the stress of 200 mOsm/kg hypotonicity. Normal cervical epithelia readjusted their volume less efficiently even in face of 250 mOsm/kg hypotonicity, and totally lost this ability in 200 mOsm/kg hypotonicity. The Cl- channel blockers affected RVD of cancer cells in a dose-dependent manner while K+ channel blockers showed no effect on RVD process of cancer cells. Furthermore, GTP/S facilitated the process of RVD, while pertussis toxin retarded it. On the other hand, neither Cl- channel blocker- DIDS, nor GTPrS or pertussis toxin showed effect on the RVD processes of HPV-immortalized and normal cervical cells, whereas K+ channel blockers such as quinidine and barium significantly blocked their RVD processes. Moreover, RVD in HPV-immortalized cells was inhibited by apamin, while RVD was not affected by apamin in normal cervical cells. These results suggest that human cervical cells with greater extent of malignant potential were more able to respond to more hypotonic stress. Furthermore, the mechanisms of RVD in different cervical cells are mediated by different ion channels. To confirm and extend this association in other cell-type, we investigated the capacity of RVD in Ha-ras transfromed NIH3T3 cells. The results showed that NIH3T3 cells with greater tumor potential were able to respond to more hypotonic stress. Together, our findings demonstrated the association between RVD capacity and extent of tumor potential in human cervical cells and NIH3T3 cells systems.
|出版狀態||Published - 1997 十二月 1|
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