title: Anticancer agent shikonin is an incompetent inducer of cancer drug resistance.
abstract: OBJECTIVE
  Cancer drug resistance is a major obstacle for the success of chemotherapy. Since most clinical anticancer drugs could induce drug resistance, it is desired to develop candidate drugs that are highly efficacious but incompetent to induce drug resistance. Numerous previous studies have proven that shikonin and its analogs not only are highly tumoricidal but also can bypass drug-transporter and apoptotic defect mediated drug resistance. The purpose of this study is to investigate if or not shikonin is a weak inducer of cancer drug resistance.
  
  
  METHODS
  Different cell lines (K562, MCF-7, and a MDR cell line K562/Adr), after repeatedly treated with shikonin for 18 months, were assayed for drug resistance and gene expression profiling.
  
  
  RESULTS
  After 18-month treatment, cells only developed a mere 2-fold resistance to shikonin and a marginal resistance to cisplatin and paclitaxel, without cross resistance to shikonin analogs and other anticancer agents. Gene expression profiles demonstrated that cancer cells did strongly respond to shikonin treatment but failed to effectively mobilize drug resistant machineries. Shikonin-induced weak resistance was associated with the up-regulation of βII-tubulin, which physically interacted with shikonin.
  
  
  CONCLUSIONS
  Taken together, apart from potent anticancer activity, shikonin and its analogs are weak inducers of cancer drug resistance and can circumvent cancer drug resistance. These merits make shikonin and its analogs potential candidates for cancer therapy with advantages of avoiding induction of drug resistance and bypassing existing drug resistance.
authors.affiliation: Cancer Institute, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
authors.forename: Qiangrong
authors.initials: Q
authors.lastname: Pan
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.forename: Danqing
authors.initials: D
authors.lastname: Hu
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D009285:Naphthoquinones / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C016101:shikonin; D017239:Paclitaxel; D002945:Cisplatin