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. 2016 Nov;49(5):1839-1847.
doi: 10.3892/ijo.2016.3685. Epub 2016 Sep 6.

Heat Shock Protein 27 Is a Potential Indicator for Response to YangZheng XiaoJi and Chemotherapy Agents in Cancer Cells

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Free PMC article

Heat Shock Protein 27 Is a Potential Indicator for Response to YangZheng XiaoJi and Chemotherapy Agents in Cancer Cells

Sioned Owen et al. Int J Oncol. .
Free PMC article

Abstract

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.

Figures

Figure 1
Figure 1
(A) Detection of HSP27 and phospho-HSP27 in SKMES1 lung cancer cells after treatment with DME-25 a YZXJ extract. (B) Changes in HSP27 and phospho-HSP27 in PANC-1 pancreatic cancer cells after treatment with DME-25 a YZXJ extract.
Figure 2
Figure 2
(A) Staining of phosphorylated HSP27 (S86) in SKMES1 human lung cancer cells (top panel) and pancreatic cancer PANC1 (bottom) after treatment with DME-25. In the control, phospho-HSP27 was seen predominantly in the focal adhesion complex regions (white arrows). Treatment with YZXJ extract DME25 resulted in almost complete loss of phospho-HSP27 from the focal adhesion complex (pink arrows). (B) Effects of DME-25 on HSP27 and its activation in SKMES1 cells as shown by western blotting. (C) Effects of DME-25 on HSP27 and its activation in PANC1 cells as shown by western blotting.
Figure 3
Figure 3
(A) Co-staining phospho-HSP27 and caspase-9 in human lung cancer SKMES-1 cells. Control cells displayed high levels of staining of both phospho-HSP27 and caspase-9, both also showing a high degree of co-localisation (white arrows). However, the co-localisation was eliminated by DME25 (bottom images). (B) Images under a higher power showing focal adhesion (FAC) and pseudopodia within the SKMES-1 cells.
Figure 4
Figure 4
(A) Co-staining phospho-HSP27 and phalloidin in human wild-type ovarian cancer A2780 (top panel) and A2780-CP70 (bottom panel) cells. (B) The co-localisation between phospho-HSP27 and caspase-9 was shown in the respective two cell lines A2780 (top panel) and A2780-CP70 (bottom panel). DME25 is the extract from YZXJ.
Figure 5
Figure 5
Co-staining phospho-HSP27 and Phalloidin in human lung cancer SKMES-1 cells.
Figure 6
Figure 6
Wild-type A2780 and cisplatin resistance A2780/CP70 responded differently to cisplatin.
Figure 7
Figure 7
(A and B) Effects of knocking down HSP27 on the migration of SKMES1 cells. (C) The knockdown also increased the sensitivity of cancer cells to low concentration of drugs, in particular when combined with DME25. (D) Effects of knocking down HSP27 on the migration of PANC-1 cells which is further decreased in the presence of DME25.

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