[Effect of bcl-2 antisense oligonucleotides on multidrug resistance of cultured uveal melanoma cells].
OBJECTIVE
To evaluate the chemotherapeutic sensitivity of uveal melanoma in vitro and reverse its drug resistance by the delivery of bcl-2 antisense oligodeoxynucleotide (AS-ODN).


METHODS
The drug sensitivity tests of primary cultured uveal melanoma cells toward 5-flurouracil (5-FU), thiophosphamide (TSPA), cisplatin (DDP), adriamycin (ADM), vinblastine (VLB), dacarbazine (DTIC) were performed with 3, -4, 5 dimethyliazol-2,5 diphenyl tetrazolium bromide (MTT). AS-ODN bcl-2 were delivered with cationic lipid to down-regulate bcl-2 expression. Immunohistochemistry and Western-blot methods were used to detect bcl-2 expression. According to the principle of multi-drug mutual action, the influence of anti-apoptosis gene bcl-2 on tumor cell drug sensitivity was measured.


RESULTS
Uveal melanoma was resistant to different chemotherapeutic drugs in different degrees. AS-ODN bcl-2 could down-regulate bcl-2 expression, was synergetic with all tested drugs and partially reversed the multi-drug resistance.


CONCLUSIONS
Clinically, with ordinary dosages the above 6 drugs have little cytotoxicity to uveal melanoma cells, bcl-2 over-expression is associated with multi-drug resistance and AS-ODN bcl-2 can partially reverse the multi-drug resistance.
Guo
Lin-jie
LJ
Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Wu
Zhong-yao
ZY
Zhang
Sheng
S
Zheng
Jian-liang
JL
Zheng
Hu-ling
HL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2