Combination of targeting CD24 and inhibiting autophagy suppresses the proliferation and enhances the apoptosis of colorectal cancer cells

Zhuo,Jingwei; Wang,Xinying

doi:10.3892/mmr.2019.10288

Combination of targeting CD24 and inhibiting autophagy suppresses the proliferation and enhances the apoptosis of colorectal cancer cells

Authors:
- Jingwei Zhuo
- Xinying Wang
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Affiliations: Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
Published online on: May 23, 2019 https://doi.org/10.3892/mmr.2019.10288
Pages: 539-548
Copyright: © Zhuo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CD24 can regulate angiogenesis, drug sensitivity and the progression of colorectal cancer (CRC). However, whether CD24 regulates autophagy and apoptosis in CRC cells remains to be fully elucidated. The present study investigated the functional role of the altered expression of CD24 in the autophagy and apoptosis of HCT116 and HT29 human CRC cells. The results revealed lower expression levels of CD24 in HCT116 cells but higher levels in HT29 cells. Inducing the overexpression or the knockdown of CD24 did not affect the viability or spontaneous apoptosis of HCT116 and HT29 cells, respectively. Induction of the overexpression of CD24 significantly decreased the relative expression levels of Beclin‑1, autophagy‑related (Atg)3 and Atg5, and the numbers of microtubule‑associated protein‑1 light chain‑3 (LC3)‑positive puncta, but increased the expression of p62 in HCT116 cells. By contrast, CD24 silencing increased the expression of Beclin‑1, Atg3 and Atg5, and the numbers of LC3‑positive puncta, but decreased the expression of p62 in HT29 cells. Treatment with 3‑methyladenine, or the knockdown of Atg5 by specific small interfering RNA to attenuate autophagy significantly enhanced the viability of CD24‑overexpressing HCT116 cells, but reduced the viability of CD24‑silenced HT29 cells, relative to their controls. As a result, the attenuation of autophagy significantly decreased the frequency of apoptotic CD24‑overexpressing HCT116 cells, but increased the percentages of apoptotic CD24‑silenced HT29 cells. The overexpression of CD24 promoted the activation of nuclear factor (NF)‑κBp65, whereas CD24 silencing attenuated its activation in CRC cells. Inhibition of the activation of NF‑κB enhanced the CD24 overexpression‑induced decrease in autophagy, but attenuated the CD24 silencing‑induced increase in autophagy in CRC cells. Therefore, CD24 inhibited the autophagy of CRC cells, and the combination of targeting CD24 and inhibiting autophagy promoted the apoptosis of CRC cells. Conceivably, these findings may aid in the design of novel therapies for the intervention of CRC.

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