Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells.
Heat shock protein 27 (HSP27) is a member of the heat shock protein family which has been linked to tumour progression and, most interestingly, to chemotherapy resistance in cancer patients. The present study examined the potential interplay between HSP27 and YangZheng XiaoJi, a traditional Chinese medicine used in cancer treatment. A range of cell lines from different tumour types including pancreatic, lung, gastric, colorectal, breast, prostate and ovarian cancer (both wild-type and resistant) were used. Levels and activation of HSP27 and its potential associated signalling pathways were evaluated by protein array and western blotting. Knockdown of HSP27 in cancer cells was achieved using siRNA. Localisation and co-localisation of HSP27 and other proteins were carried out by immunofluorescence. Cell growth and migration were evaluated in their response to a range of chemotherapeutic agents. The present study first identified, by way of protein array, that YangZheng XiaoJi was able to inhibit the phosphorylation of HSP27 protein in cancer cells. We further demonstrated that HSP27, which is co-localised with caspase-9, can be blocked from localising in focal adhesions and co-localising with caspase-9 by YangZheng XiaoJi. The study also demonstrated that YangZheng XiaoJi was able to sensitise cancer cells including those cells that were resistant to chemotherapy, to chemotherapeutic agents. Finally, knocking down HSP27 markedly reduced the migration of cancer cells and increased the sensitivity of cancer cells to the inhibitory effect on cellular migration by YangZheng XiaoJi. YangZheng XiaoJi can act as an agent in first sensitising cancer cells to chemotherapy and secondly to overcome, to some degree, chemoresistance when used in an appropriate fashion in patients who have active HSP27.
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, UK.
Sioned
S
Owen
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, UK.
Huishan
H
Zhao
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, UK.
Alwyn
A
Dart
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, UK.
Yamei
Y
Wang
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, UK.
Fiona
F
Ruge
Yiling Medical Research Institute, Shijiazhuang, Hebei, P.R. China.
Yong
Y
Gao
Yiling Medical Research Institute, Shijiazhuang, Hebei, P.R. China.
Cong
C
Wei
Yiling Medical Research Institute, Shijiazhuang, Hebei, P.R. China.
Yiling
Y
Wu
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, UK.
Wen G
WG
Jiang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053453:Caspase 9 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010936:Plant Extracts; D034741:RNA, Small Interfering; C579032:yangzheng xiaoji; D053453:Caspase 9