Abstract
Autophagy is a survival mechanism that is activated in response to nutrient deprivation. The link between aberrant autophagy and cancer has been increasingly recognized. Survivin, an anti-apoptotic molecule, and the autophagy pathway are correlated with therapeutic responses to cancer. However, the role of autophagy in cancer progression remains unclear. Here, we generated survivin knockdown cells (survivin-KD) by introducing a short interfering RNA (siRNA) into hepatocellular carcinoma (HCC) cells, and we observed a 20 % reduction in the survival of these survivin- KD cells, as determined by MTT assay. In addition, an increased number of stress granules, increased positive staining by acridine orange and a shift in the high side scatter (SSC) cell population in flow cytometry analysis were observed in survivin-KD cells. Furthermore, electronmicroscopy revealed an increased number of autophagosomes in survivin-KD cells compared with scrambled control cells. Finally, we treated cells with an autophagy inhibitor, 3-MA, and observed a decrease in cell survival in survivin-KD cells compared with scrambled control cells. Our study suggests that an autophagy signal may be activated after the anti-apoptotic molecule survivin is suppressed. This finding implies that autophagy may be an alternative survival pathway in HCC cells and may provide a basis for the development of new therapeutic strategies for HCC.
| Original language | English |
|---|---|
| Pages (from-to) | 9957-9966 |
| Number of pages | 10 |
| Journal | Tumor Biology |
| Volume | 35 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Jul 10 2014 |
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Keywords
- Anti-proliferation
- Autophagy
- HCC
- Survivin
ASJC Scopus subject areas
- Cancer Research
- Medicine(all)
Cite this
Silencing survivin activates autophagy as an alternative survival pathway in HCC cells. / Chang, Yu Jia; Li, Li Tzu; Chen, Hsin An; Hung, Chin Sheng; Wei, Po Li.
In: Tumor Biology, Vol. 35, No. 10, 10.07.2014, p. 9957-9966.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Silencing survivin activates autophagy as an alternative survival pathway in HCC cells
AU - Chang, Yu Jia
AU - Li, Li Tzu
AU - Chen, Hsin An
AU - Hung, Chin Sheng
AU - Wei, Po Li
PY - 2014/7/10
Y1 - 2014/7/10
N2 - Autophagy is a survival mechanism that is activated in response to nutrient deprivation. The link between aberrant autophagy and cancer has been increasingly recognized. Survivin, an anti-apoptotic molecule, and the autophagy pathway are correlated with therapeutic responses to cancer. However, the role of autophagy in cancer progression remains unclear. Here, we generated survivin knockdown cells (survivin-KD) by introducing a short interfering RNA (siRNA) into hepatocellular carcinoma (HCC) cells, and we observed a 20 % reduction in the survival of these survivin- KD cells, as determined by MTT assay. In addition, an increased number of stress granules, increased positive staining by acridine orange and a shift in the high side scatter (SSC) cell population in flow cytometry analysis were observed in survivin-KD cells. Furthermore, electronmicroscopy revealed an increased number of autophagosomes in survivin-KD cells compared with scrambled control cells. Finally, we treated cells with an autophagy inhibitor, 3-MA, and observed a decrease in cell survival in survivin-KD cells compared with scrambled control cells. Our study suggests that an autophagy signal may be activated after the anti-apoptotic molecule survivin is suppressed. This finding implies that autophagy may be an alternative survival pathway in HCC cells and may provide a basis for the development of new therapeutic strategies for HCC.
AB - Autophagy is a survival mechanism that is activated in response to nutrient deprivation. The link between aberrant autophagy and cancer has been increasingly recognized. Survivin, an anti-apoptotic molecule, and the autophagy pathway are correlated with therapeutic responses to cancer. However, the role of autophagy in cancer progression remains unclear. Here, we generated survivin knockdown cells (survivin-KD) by introducing a short interfering RNA (siRNA) into hepatocellular carcinoma (HCC) cells, and we observed a 20 % reduction in the survival of these survivin- KD cells, as determined by MTT assay. In addition, an increased number of stress granules, increased positive staining by acridine orange and a shift in the high side scatter (SSC) cell population in flow cytometry analysis were observed in survivin-KD cells. Furthermore, electronmicroscopy revealed an increased number of autophagosomes in survivin-KD cells compared with scrambled control cells. Finally, we treated cells with an autophagy inhibitor, 3-MA, and observed a decrease in cell survival in survivin-KD cells compared with scrambled control cells. Our study suggests that an autophagy signal may be activated after the anti-apoptotic molecule survivin is suppressed. This finding implies that autophagy may be an alternative survival pathway in HCC cells and may provide a basis for the development of new therapeutic strategies for HCC.
KW - Anti-proliferation
KW - Autophagy
KW - HCC
KW - Survivin
UR - http://www.scopus.com/inward/record.url?scp=84922395247&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922395247&partnerID=8YFLogxK
U2 - 10.1007/s13277-014-2257-6
DO - 10.1007/s13277-014-2257-6
M3 - Article
C2 - 25008566
AN - SCOPUS:84922395247
VL - 35
SP - 9957
EP - 9966
JO - Tumor Biology
JF - Tumor Biology
SN - 1010-4283
IS - 10
ER -