title: A Potent Chemotherapeutic Strategy with Eg5 Inhibitor against Gemcitabine Resistant Bladder Cancer.
abstract: Development of resistance to gemcitabine is a major concern in bladder cancer therapy, and the mechanism remains unclear. Eg5 has been recently identified as an attractive target in cancer chemotherapy, so novel targeted chemotherapy with Eg5 inhibitor is expected to improve the anticancer effect in gemcitabine-resistant bladder cancer. In this research, RT112-Gr cells were 350-fold less sensitive to gemcitabine than the parental cell lines, while KU7-Gr cells were 15-fold less sensitive to gemcitabine than the parental cell lines. Human OneArray Microarray analysis was performed to obtain broad spectrum information about the genes differentially expressed in RT112 and RT112-Gr cells. The anti-proliferative activity of S(MeO)TLC, an Eg5 inhibitor, was analyzed in RT112-Gr cell lines using a cell viability assay. Furthermore, the inhibitory effect was evaluated in vivo using subcutaneous xenograft tumor model. According to the result of Human OneArray GeneChip, RRM1 and RRM2 were up-regulated, while there was no significant change in Eg5. Trypan blue staining confirmed that in S(MeO)TLC and Gemcitabine combining S(MeO)TLC group cell viability were significantly decreased in RT112-Gr cells as compared with other groups. S(MeO)TLC and S(MeO)TLC+gemcitabine groups prominently suppressed tumor growth in comparison with other groups' in vivo. There were no significant differences in S(MeO)TLC and gemcitabine+S(MeO)TLC group in the effect of inhibition of bladder cancer in vivo and in vitro. Our data collectively demonstrated that S(MeO)TLC represents a novel strategy for the treatment of gemcitabine resistant bladder cancer.
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.|Department of Cardiac Surgery, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ShanDong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Jiaju
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Kejia
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Dongbin
authors.initials: D
authors.lastname: Bi
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Zuohui
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ShanDong, China.
authors.forename: Sentai
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012262:Ribonucleoside Diphosphate Reductase / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism; D014320:Triphenylmethyl Compounds / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: C470243:KIF11 protein, human; C000594388:S-(methoxytrityl)cysteine; D014320:Triphenylmethyl Compounds; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C093713:ribonucleotide reductase M2; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D016547:Kinesins; D003545:Cysteine; D000093542:Gemcitabine