[Relationship between the expression of P-glycoprotein, glutathione S-transferase-pi and thymidylate synthase proteins and adenosine triphosphate tumor chemosensitivity assay in cervical cancer].
OBJECTIVE
To explore the feasibility of the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in human cervical cancer chemosensitivity testing and to analyze the relationship between the three drug resistance-associated proteins: P-glycoprotein (P-gp); glutathione S-transferase-pi (GST-pi); thymidylate synthase (TS) and ATP-TCA.


METHODS
ATP-TCA was used to detect the sensitivity of 35 specimens of fresh cervical cancer to six cytotoxic drugs as follows: paclitaxel (TAX), cisplatin (DDP), bleomycin (BLM), gemcitabine (GEM), 5-fluorouracil (5-FU), irinotecan (CPT-11). Consecutive sections from 35 cases of cervical cancer were assessed immunohistochemically for expression of P-gp, GST-pi and TS proteins.


RESULTS
(1) Thirty-two of 35 assays were completed successfully, with an evaluability rate of ATP-TCA at 91% (32/35). There was a marked heterogeneity of chemosensitivity in cervical cancer. The ex vivo sensitive rate of TAX was 88% (28/32), of 5-FU 72% (23/32), of GEM 62% (20/32), of DDP 19% (6/32), of BLM 16% (5/32), and of CPT-11 12% (4/32). (2) The expression of GST-pi and TS protein in cervical cancer was 66% (21/32) and 44% (14/32), which was associated with the resistance to DDP and 5-FU ex vivo (P=0.011, P=0.022), respectively; but the expression of P-gp protein was not associated with any resistance to TAX, 5-FU, GEM, DDP, BLM or CPT-11 ex vivo (P>0.05).


CONCLUSIONS
ATP-TCA could be used to individualize chemotherapy by selecting agents for particular patients of cervical cancer. The expression of GST-pi and TS protein might be useful biomarkers to predict the resistance to DDP and 5-FU in patients with cervical cancer.
Gao
Guo-lan
GL
Department of Gynecologic Oncology, Jiangxi Tumor Hospital, Nanchang 330029, China.
Wan
Hong-ying
HY
Zou
Xue-sen
XS
Chen
Wen-xue
WX
Chen
Yue-qing
YQ
Huang
Xiu-zhen
XZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000255:Adenosine Triphosphate; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000378:metabolism / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D017239:Paclitaxel / Q000378:metabolism / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001761:Bleomycin; D000255:Adenosine Triphosphate; D013940:Thymidylate Synthase; D051549:Glutathione S-Transferase pi; D017239:Paclitaxel; D002945:Cisplatin