title: In Vitro and In Vivo Effects of Jia-Wei-Xiao-Yao-San in Human Breast Cancer MCF-7 Cells Treated With Tamoxifen.
abstract: BACKGROUND
  There is epidemiological evidence that Jia-Wei-Xiao-Yao-San (JWXYS) is the most common Chinese medicine decoction coprescribed with tamoxifen (Tam) when breast cancer is treated by hormonal therapy. However, whether there is interaction between JWXYS and Tam remains to be clarified. The aim of this study was to investigate the in vitro and in vivo effects of JWXYS on human breast cancer MCF-7 cells treated with Tam.
  
  
  METHODS
  In vitro cultured MCF-7 cells were cotreated with JWXYS and Tam. This was followed by MTT ([4,5-cimethylthiazol-2-yl]- 2,5-diphenyl tetrazolium bromide) assays and cell cycle analysis to assess cell proliferation; Western blot analysis was used to analyze the expression of various proteins involved in growth-related signal pathways. In addition, immunohistochemistry was used to detect autophagy among the cancer cells. In vivo analysis used female athymic nude mice implanted with MCF-7 cells; these mice were randomly assigned to 6 groups. All mice were killed humanely after 21 days of treatment; body weight, tumor volume, and tumor weight were then measured.
  
  
  RESULTS
  JWXYS was not cytotoxic to MCF-7 cells, based on the fact that there were no statistically significant changes between the JWXYS + Tam groups and the Tam-alone group in cell numbers, cell cycle progression, and cell proliferation signals, the latter including the expression levels of AKT, ERK, P38, p27(Kip1), and light chain (LC3)-I, II. Furthermore, using the MCF-7 xenograft mouse model, there were no significant changes between the JWXYS (1.3-3.9 gm/kg) + Tam groups and the Tam-alone group in terms of tumor weight and the protein expression levels of AKT, ERK, P38, and p27 (Kip1). However, there was a significant decrease in LC3-II protein expression with the low-dose JWXYS + Tam group but not with the middle- or high-dose JWXYS + Tam groups compared with the Tam-alone group.
  
  
  CONCLUSIONS
  Based on in vitro studies and in vivo functional studies, there is no obvious interaction between JWXYS and Tam. However, the presence of interference at the molecular level in relation to LC3-II expression provides important information and may affect treatment strategies when physicians have patients with estrogen receptor-α(+) or progesterone receptor(+) breast cancers.
authors: National Yang-Ming University, Taiwan, ROC Chang Gung University, Taoyuan, Taiwan, ROC Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors: Jiun-Liang
authors: JL
authors: Chen
authors: National Taiwan Ocean University, Taiwan, ROC.
authors: Chun-Ju
authors: CJ
authors: Chang
authors: Taipei Veterans General Hospital, Taiwan, ROC.
authors: Jir-You
authors: JY
authors: Wang
authors: Cheng-Hsin General Hospital, Taipei, Taiwan, ROC.
authors: Che-Sheng
authors: CS
authors: Wen
authors: National Yang-Ming University, Taiwan, ROC Taipei Veterans General Hospital, Taiwan, ROC.
authors: Ling-Ming
authors: LM
authors: Tseng
authors: National Yang-Ming University, Taiwan, ROC.
authors: Wen-Chi
authors: WC
authors: Chang
authors: National Yang-Ming University, Taiwan, ROC.
authors: Nattanant
authors: N
authors: Noomhorm
authors: National Yang-Ming University, Taiwan, ROC.
authors: Hui-Ju
authors: HJ
authors: Liu
authors: Taipei Veterans General Hospital, Taiwan, ROC.
authors: Wei-Shone
authors: WS
authors: Chen
authors: National Yang-Ming University, Taiwan, ROC Taipei Veterans General Hospital, Taiwan, ROC Cheng-Hsin General Hospital, Taipei, Taiwan, ROC chiujh@mailsrv.ym.edu.tw.
authors: Jen-Hwey
authors: JH
authors: Chiu
authors: Taipei Veterans General Hospital, Taiwan, ROC.
authors: Yi-Ming
authors: YM
authors: Shyr
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004365:Drugs, Chinese Herbal; C103354:kamisyoyo san; D013629:Tamoxifen
keywords: Jia-Wei-Xiao-Yao-San; breast cancer; herbs; interaction; tamoxifen