[ASPP2 inhibits oxaliplatin-induced autophagy and promotes apoptosis of colon cancer cells].

Abstract

OBJECTIVE:

To investigate the role of apoptosis stimulating p53 binding protein 2 (ASPP2)-induced p53-dependent and p53-independent autophagy inhibition in apoptosis-promoting function of oxaliplatin (OXA).

METHODS:

According to different treatments, HCT116(p53(-/-)) cells were divided into 6 groups: rapamycin combined with ASPP2 group, ASPP2 group, p53 group, ASPP2 combined with p53 group, OXA combined with 3-methyladenine (3-MA) group, control group (OXA treatment or starvation without OXA treatment). When the level of apoptosis was detected, green fluorescent protein-advirus (GFP-Ad) group and rapamycin group were supplemented as controls. Cells were transfected with GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) plasmid, and LC3-expressing cells were calculated under a fluorescent microscope. Expressions of autophagy-related molecules were detected by Western blotting. Cells were subjected to annexin V-FITC/PI staining and apoptosis was assessed by flow cytometry.

RESULTS:

The 3-MA group showed the same inhibitory ability on autophagy with the ASPP2 group, and both of them were able to promote OXA or starvation-induced apoptosis, but the cell apoptosis rate in the 3-MA group was lower than that of the ASPP2 group. Rapamycin combined with ASPP2 still promoted OXA or starvation-induced apoptosis, and the apoptosis rate was also lower than that of the ASPP2 group. However, rapamycin counteracted effectively the inhibitory effect of ASPP2 on autophagy.

CONCLUSION:

OXA can induce autophagy of colorectal cancer cells, while ASPP2 over-expression can suppress the OXA-induced autophagy. ASPP2 can promote apoptosis through p53-dependent and p53-independent pathways. The function of ASPP2 promoting cell apoptosis through p53-dependent and p53-independent pathways is not entirely achieved by inhibiting cell autophagy.

• Authors: Bishi Wang, Luxin Qiao, Ying Shi, Xiaokun Feng, Dexi Chen, Hongliang Guo
• Journal: Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) Vol. 31 Issue 7 Pg. 898-904 (Jul 2015) ISSN: 1007-8738 [Print] China
• PMID: 26146058 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Organoplatinum Compounds
• TP53BP2 protein, human
• Tumor Suppressor Protein p53
• Oxaliplatin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Autophagy (drug effects)
• Colonic Neoplasms (pathology)
• HCT116 Cells
• Humans
• Organoplatinum Compounds (pharmacology)
• Oxaliplatin
• Tumor Suppressor Protein p53 (deficiency, metabolism)