PFKFB3 Inhibition Attenuates Oxaliplatin-Induced Autophagy and Enhances Its Cytotoxicity in Colon Cancer Cells
Identifieur interne : 000559 ( Main/Exploration ); précédent : 000558; suivant : 000560PFKFB3 Inhibition Attenuates Oxaliplatin-Induced Autophagy and Enhances Its Cytotoxicity in Colon Cancer Cells
Auteurs : Siyuan Yan ; Nan Zhou ; Deru Zhang ; Kaile Zhang ; Wenao Zheng ; Yonghua Bao ; Wancai Yang [États-Unis]Source :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2019.
Abstract
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), a glycolytic enzyme highly expressed in cancer cells, has been reported to participate in regulating metabolism, angiogenesis, and autophagy. Although anti-cancer drug oxaliplatin (Oxa) effectively inhibits cell proliferation and induces apoptosis, the growing resistance and side-effects make it urgent to improve the therapeutic strategy of Oxa. Although Oxa induces the autophagy process, the role of PFKFB3 in this process remains unknown. In addition, whether PFKFB3 affects the cytotoxicity of Oxa has not been investigated. Here, we show that Oxa-inhibited cell proliferation and migration concomitant with the induction of apoptosis and autophagy in SW480 cells. Both inhibition of autophagy by small molecule inhibitors and siRNA modification decreased the cell viability loss and apoptosis induced by Oxa. Utilizing quantitative PCR and immunoblotting, we observed that Oxa increased PFKFB3 expression in a time- and dose-dependent manner. Meanwhile, suppression of PFKFB3 attenuated both the basal and Oxa-induced autophagy, by monitoring the autophagic flux and phosphorylated-Ulk1, which play essential roles in autophagy initiation. Moreover, PFKFB3 inhibition further inhibited the cell proliferation/migration, and cell viability decreased by Oxa. Collectively, the presented data demonstrated that PFKFB3 inhibition attenuated Oxa-induced autophagy and enhanced its cytotoxicity in colorectal cancer cells.
Url:
DOI: 10.3390/ijms20215415
PubMed: 31671668
PubMed Central: 6862230
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), a glycolytic enzyme highly expressed in cancer cells, has been reported to participate in regulating metabolism, angiogenesis, and autophagy. Although anti-cancer drug oxaliplatin (Oxa) effectively inhibits cell proliferation and induces apoptosis, the growing resistance and side-effects make it urgent to improve the therapeutic strategy of Oxa. Although Oxa induces the autophagy process, the role of PFKFB3 in this process remains unknown. In addition, whether PFKFB3 affects the cytotoxicity of Oxa has not been investigated. Here, we show that Oxa-inhibited cell proliferation and migration concomitant with the induction of apoptosis and autophagy in SW480 cells. Both inhibition of autophagy by small molecule inhibitors and siRNA modification decreased the cell viability loss and apoptosis induced by Oxa. Utilizing quantitative PCR and immunoblotting, we observed that Oxa increased PFKFB3 expression in a time- and dose-dependent manner. Meanwhile, suppression of PFKFB3 attenuated both the basal and Oxa-induced autophagy, by monitoring the autophagic flux and phosphorylated-Ulk1, which play essential roles in autophagy initiation. Moreover, PFKFB3 inhibition further inhibited the cell proliferation/migration, and cell viability decreased by Oxa. Collectively, the presented data demonstrated that PFKFB3 inhibition attenuated Oxa-induced autophagy and enhanced its cytotoxicity in colorectal cancer cells.</p>
</div>
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<author><name sortKey="Li, Q" uniqKey="Li Q">Q. Li</name>
</author>
<author><name sortKey="Li, H" uniqKey="Li H">H. Li</name>
</author>
<author><name sortKey="Zhang, C" uniqKey="Zhang C">C. Zhang</name>
</author>
</analytic>
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</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Illinois</li>
</region>
<settlement><li>Chicago</li>
</settlement>
<orgName><li>Université de l'Illinois à Chicago</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Bao, Yonghua" sort="Bao, Yonghua" uniqKey="Bao Y" first="Yonghua" last="Bao">Yonghua Bao</name>
<name sortKey="Yan, Siyuan" sort="Yan, Siyuan" uniqKey="Yan S" first="Siyuan" last="Yan">Siyuan Yan</name>
<name sortKey="Zhang, Deru" sort="Zhang, Deru" uniqKey="Zhang D" first="Deru" last="Zhang">Deru Zhang</name>
<name sortKey="Zhang, Kaile" sort="Zhang, Kaile" uniqKey="Zhang K" first="Kaile" last="Zhang">Kaile Zhang</name>
<name sortKey="Zheng, Wenao" sort="Zheng, Wenao" uniqKey="Zheng W" first="Wenao" last="Zheng">Wenao Zheng</name>
<name sortKey="Zhou, Nan" sort="Zhou, Nan" uniqKey="Zhou N" first="Nan" last="Zhou">Nan Zhou</name>
</noCountry>
<country name="États-Unis"><region name="Illinois"><name sortKey="Yang, Wancai" sort="Yang, Wancai" uniqKey="Yang W" first="Wancai" last="Yang">Wancai Yang</name>
</region>
</country>
</tree>
</affiliations>
</record>
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