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Cisplatin restores p53 function and enhances the radiosensitivity in HPV16 E6 containing SiHa cells
Author(s) -
Huang Haimei,
Huang ShianYi,
Chen TingTing,
Chen JaChi,
Chiou ChianLing,
Huang TerMei
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10769
Subject(s) - cisplatin , apoptosis , radiosensitivity , transfection , cytotoxicity , chemistry , microbiology and biotechnology , cancer research , in vitro , biology , radiation therapy , gene , chemotherapy , medicine , biochemistry , genetics
Most HPV‐positive cervical cancer cells possess wild type p53 gene, but its normal p53 functions are disrupted by expression of HPVs E6. Treatment with 0–20 μM cisplatin for 24 h in HPV16 E6 containing SiHa cells suppressed E6 mRNA, reduced E6 protein, and restored p53 expression in dose‐dependent manners. Dual‐parameter flow cytometric analysis indicated that sub‐G 1 apoptotic cells, but not necrotic cells were the major species for cisplatin‐induced cytotoxicity in SiHa cells. After 0–10 μM cisplatin treatment, slightly more apoptotic cells appeared from SiHa cells than those from dominant negative p53‐transfected SiHa cells. There was no different ionizing radiation (IR)‐induced apoptosis in these two different cells. On the other hand, cisplatin enhanced more IR‐induced sub‐G 1 apoptosis in SiHa than mp53‐SiHa cells. These accompanied with prolonged p53 restoration in irradiated‐SiHa cells after 24 h cisplatin treatment and thereafter. In contrast, it was not found in cells after irradiation alone. Similar results were also shown in Mdm2 expression in SiHa cells after combined treatment. Therefore, cisplatin restored p53 expression and prolonged IR‐induced p53 restoration would be possible candidates to response more sub‐G 1 apoptosis in irradiated SiHa cells. These results provided another new explanation on cisplatin sensitizing radiotherapy for HPV16 E6 containing cancer cells. © 2004 Wiley‐Liss, Inc.