Histology and histopathology · 2025
Effect of ART1 on the efficacy of oxaliplatin in colorectal cancer under high-cholesterol conditions.
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Chen Xiaodan, Zhang Shuxian, Huang Jing, Gong Qian, Cao Xingliang, Xie Saiwei, Xiao Ming, Tang Yi, Li Ming, Li Qingshu, Wang Yalan
Аннотация
BACKGROUND: The growth of colorectal cancer (CRC) can be affected by cholesterol (CHO), which may inhibit the efficacy of oxaliplatin (OXA). A high-fat diet can upregulate phosphorylation by sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P)/sphingosine 1-phosphate receptor 1 (S1PR1) and promote tumour cell proliferation. Moreover, S1P activates signal transducer and activator of transcription 3 (STAT3), which plays a critical role in tumour cell proliferation. Knockdown of arginine-specific single ADP ribosyltransferase 1 (ART1) can delay the growth of CRC and promote the inhibitory effect of OXA on CRC cell proliferation. Consequently, in a high-CHO environment, this study aims to investigate the impact of ART1 knockdown in CRC cells treated with OXA and on the growth of transplanted tumours in mice in vivo.
METHODS: Immunohistochemistry of CRC tissue revealed that, compared with that of normal blood lipids, ART1 expression in CRC tissue from patients with hypercholesterolaemia was higher. Based on CCK8 and EdU assays, we found that ART1 knockdown reduced the proliferation ability of CRC cells and decreased the volume of subcutaneously transplanted tumours in the high-CHO group. Finally, under high-CHO conditions, ART1 knockdown significantly reduced the protein expression levels of SPHK1, S1P, S1PR1, STAT3, and p-STAT3 in CT26 cells and transplanted tumours, as determined by western blotting.
RESULTS: These findings suggest that under high-CHO conditions, inhibition of ART1 expression can promote the inhibitory effect of OXA on CT26 cell proliferation, which may be related to the influence of ART1 on STAT3 expression through SPHK1/S1P/S1PR1.
CONCLUSIONS: This study is of great significance in improving the inhibitory effect of OXA on CRC cell proliferation in a high-CHO environment.
METHODS: Immunohistochemistry of CRC tissue revealed that, compared with that of normal blood lipids, ART1 expression in CRC tissue from patients with hypercholesterolaemia was higher. Based on CCK8 and EdU assays, we found that ART1 knockdown reduced the proliferation ability of CRC cells and decreased the volume of subcutaneously transplanted tumours in the high-CHO group. Finally, under high-CHO conditions, ART1 knockdown significantly reduced the protein expression levels of SPHK1, S1P, S1PR1, STAT3, and p-STAT3 in CT26 cells and transplanted tumours, as determined by western blotting.
RESULTS: These findings suggest that under high-CHO conditions, inhibition of ART1 expression can promote the inhibitory effect of OXA on CT26 cell proliferation, which may be related to the influence of ART1 on STAT3 expression through SPHK1/S1P/S1PR1.
CONCLUSIONS: This study is of great significance in improving the inhibitory effect of OXA on CRC cell proliferation in a high-CHO environment.