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2015 ; 47
(2
): 313-21
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Blockade of autophagy aggravates endoplasmic reticulum stress and improves
Paclitaxel cytotoxicity in human cervical cancer cells
#MMPMID25578058
Xu L
; Liu JH
; Zhang J
; Zhang N
; Wang ZH
Cancer Res Treat
2015[Apr]; 47
(2
): 313-21
PMID25578058
show ga
PURPOSE: Autophagy is one of the ways to degrade unfolded proteins after
endoplasmic reticulum (ER) stress. The purpose of this study is to determine
whether a blockade of autophagy leads to aggravated endoplasmic reticulum stress,
which then induces cells apoptosis in HeLa cells treated with paclitaxel.
MATERIALS AND METHODS: Autophagy activation and the proapoptotic effects were
characterized using monodansylcadaverine labeling and Hoechest staining,
respectively. A Western blot analysis was used to detect the expression of
apoptotic and autophagy-related genes. A flow cytometry was used to assess the
cell apoptosis ratio. RESULTS: Paclitaxel exposure induced the aggregation of
autophagosomes in the cytoplasms of cervical cancer HeLa cells. The expression of
Beclin 1 and LC3 II were upregulated, but p62 was downregulated, which suggests
that autophagy was promoted by paclitaxel. On the other hand, the expression of
GRP78 obviously increased, suggesting that ER stress was induced after paclitaxel
treatment. The cell proliferation assay indicated that a knockdown of Beclin 1
sensitized HeLa cells to paclitaxel. Furthermore, paclitaxel-mediated apoptotic
cell death was further potentiated by the pretreatment with autophagy inhibitor
chloroquine or small interfering RNA against Beclin 1. These results suggest that
an induction of autophagy by paclitaxel may induce cell survival rather than cell
death in HeLa cells; moreover, inhibition of autophagy led to an aggravated ER
stress and an induction of downstream apoptosis. CONCLUSION: Our results reveal
autophagy induced by paclitaxel conferred protection of tumor cells against
apoptosis, and blockade of autophagy subsequently aggravated ER stress, enhancing
the apoptosis associated with paclitaxel treatment in HeLa cells.