title: Reversion of multidrug resistance by SKI-II in SGC7901/DDP cells and exploration of underlying mechanisms.
abstract: In order to investigate whether SKI-II could reverse drug resistance and its possible mechanisms, we treated SGC7901/DDP cells with SKI-II or SKI-II in combination with DDP. Then cell growth, apoptosis, micro- morphological changes, and expression of SphK1, P-gp, NF-kB, Bcl-2 and Bax were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western blot assay respectively. SGC7901/DDP cells were insensitive to cisplatin 2.5 mg/L, but when pretreated with SKI-II, their proliferation was inhibited by cisplatin 2.5mg/L significantly, the inhibition rate increasing with time and dose. The apoptosis rate was also significantly elevated. Expression of SphK1 and P-gp was decreased significantly, Pearson correlation analysis showing significant correlation between the two (r=0.595, P<0.01). Expression of NF-kB and Bcl-2 was decreased significantly, while that of Bax was increased, compared to the control group. There were significant correlations between SphK1 and NF-kB(r=0.723, P<0.01), and NF-kB and Bcl-2(r=0.768, P<0.01). All these data indicated that SKI-II could reverse drug resistance of SGC7901/DDP to cisplatin by down-regulating expression of P-gp and up-regulating apoptosis through down-regulation of SphK1. The increased apoptotic sensitivity of SGC7901/ DDP to cisplatin was due to the decreasing proportion of Bcl-2/Bax via down-regulating NF-kB.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Zu-An
authors.initials: ZA
authors.lastname: Zhu
authors.forename: Zheng-Qiu
authors.initials: ZQ
authors.lastname: Zhu
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Cai
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D013844:Thiazoles / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C525025:4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol; D000970:Antineoplastic Agents; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D002945:Cisplatin