Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1.
Bleomycin is a first-line clinically used antitumor antibiotic for effective             treatment of certain types of cancer in combination with other antitumor agents.             Its action is affected by bleomycin hydrolase (BLH), DNA repair enzymes, membrane             transport proteins and other cellular factors. To clarify whether BLH confers             the resistance to bleomycin in tumor cells, it is necessary to further investigate             the roles of BLH and its combination with other factors such as caveolin-1 in             the action of bleomycin. In this study fourteen human cell lines were used for             determination of bleomycin action and roles of BLH and caveolin-1. The relationship             between action of bleomycin and cellular amount of BLH was detected by the MTT             method and western blotting in the human leukemia cell line HL-60, HeLa cervical             cancer cells and HaCaT immortalized keratinocyte cells. The sensitivity to bleomycin             was increased in HeLa cells after knockdown of BLH mRNA by RNA interference. There             is no relationship between caveolin-1 levels and action of bleomycin, although             the distribution of the cell cycle was altered in the caveolin-1-knockdown HeLa             cells after treatment with bleomycin. In addition, regulation of BLH and caveolin-1             expression in HeLa and HaCaT cells was observed in a concentration-dependent manner             after exposure to bleomycin. In conclusion, bleomycin hydrolase is one of the             biomarkers for determination of bleomycin action. Although caveolin-1 can respond             to bleomycin treatment, it is unrelated to bleomycin sensitivity.
Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
Jianguo
J
Chen
Yang
Y
Chen
Qiyang
Q
He
D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology; D001761:Bleomycin / Q000378:metabolism* / Q000494:pharmacology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D010084:Oxidation-Reduction; D034622:RNA Interference
D000903:Antibiotics, Antineoplastic; D051242:Caveolin 1; D001761:Bleomycin; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase