TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell
Background. Oxaliplatin is the first-choice chemotherapy method for patients with advanced colon cancer. However, its resistance leads to treatment failure for many patients. In our experiments, we aim to elucidate the associations among TRIM29 protein, mutant P53, and the resistance of colon cancer...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2021-01-01
|
Series: | Canadian Journal of Gastroenterology and Hepatology |
Online Access: | http://dx.doi.org/10.1155/2021/8870907 |
id |
doaj-0ea370a39a8c4d1f89fbcf247dbe2420 |
---|---|
record_format |
Article |
spelling |
doaj-0ea370a39a8c4d1f89fbcf247dbe24202021-04-05T00:01:52ZengHindawi LimitedCanadian Journal of Gastroenterology and Hepatology2291-27972021-01-01202110.1155/2021/8870907TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer CellGuoqiong Lei0Sushun Liu1Xin Yang2Chao He3Department of NeurosurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryBackground. Oxaliplatin is the first-choice chemotherapy method for patients with advanced colon cancer. However, its resistance leads to treatment failure for many patients. In our experiments, we aim to elucidate the associations among TRIM29 protein, mutant P53, and the resistance of colon cancer cells to oxaliplatin. Methods. HCT116 and HT-29 cells were cultured and transfected with plasmids pIRES2-ZsGreen1-TRIM29-flag. Western blot and real-time qRT-PCR were utilized to examine the protein and mRNA expressions of TRIM29 and other related markers, respectively. MTT assay was utilized to determine the cell growth rate and generate the inhibition curve. Continuous culture in low-concentration oxaliplatin was conducted to construct oxaliplatin-resistant cell lines. The coimmunoprecipitation method and immunofluorescence detection were used to examine the interaction between TRIM29 and mutant P53 protein in HT29 cells. Results. We successfully transfected pIRES2-ZsGreen1-TRIM29-flag into HCT116 and HT29 cells, which were utilized in the whole experiments. TRIM29 significantly increased the sensitivity of P53 mutant colon cancer cell HT29 to oxaliplatin. The oxaliplatin-resistant model of P53 mutant colon cancer cell HT29 was successfully constructed. TRIM29 physically bound with mutant P53 and retained it in the cytoplasm from the nucleus, which inhibited its transcription function of downstream genes such as MDR1. In addition, TRIM29 successfully reversed the resistance of HT29-OX resistant cell model to oxaliplatin. Conclusion. In mutant P53 colon cancer cell HT29, TRIM29 greatly increased the sensitivity of HT29 to oxaliplatin and reverse oxaliplatin resistance. The underlying mechanism is TRIM29 may increase the sensitivity of HT29 to oxaliplatin by blocking the transcriptional function of mutant P53, which inhibits the transcription function of its downstream gene such as MDR1.http://dx.doi.org/10.1155/2021/8870907 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guoqiong Lei Sushun Liu Xin Yang Chao He |
spellingShingle |
Guoqiong Lei Sushun Liu Xin Yang Chao He TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell Canadian Journal of Gastroenterology and Hepatology |
author_facet |
Guoqiong Lei Sushun Liu Xin Yang Chao He |
author_sort |
Guoqiong Lei |
title |
TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell |
title_short |
TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell |
title_full |
TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell |
title_fullStr |
TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell |
title_full_unstemmed |
TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell |
title_sort |
trim29 reverses oxaliplatin resistance of p53 mutant colon cancer cell |
publisher |
Hindawi Limited |
series |
Canadian Journal of Gastroenterology and Hepatology |
issn |
2291-2797 |
publishDate |
2021-01-01 |
description |
Background. Oxaliplatin is the first-choice chemotherapy method for patients with advanced colon cancer. However, its resistance leads to treatment failure for many patients. In our experiments, we aim to elucidate the associations among TRIM29 protein, mutant P53, and the resistance of colon cancer cells to oxaliplatin. Methods. HCT116 and HT-29 cells were cultured and transfected with plasmids pIRES2-ZsGreen1-TRIM29-flag. Western blot and real-time qRT-PCR were utilized to examine the protein and mRNA expressions of TRIM29 and other related markers, respectively. MTT assay was utilized to determine the cell growth rate and generate the inhibition curve. Continuous culture in low-concentration oxaliplatin was conducted to construct oxaliplatin-resistant cell lines. The coimmunoprecipitation method and immunofluorescence detection were used to examine the interaction between TRIM29 and mutant P53 protein in HT29 cells. Results. We successfully transfected pIRES2-ZsGreen1-TRIM29-flag into HCT116 and HT29 cells, which were utilized in the whole experiments. TRIM29 significantly increased the sensitivity of P53 mutant colon cancer cell HT29 to oxaliplatin. The oxaliplatin-resistant model of P53 mutant colon cancer cell HT29 was successfully constructed. TRIM29 physically bound with mutant P53 and retained it in the cytoplasm from the nucleus, which inhibited its transcription function of downstream genes such as MDR1. In addition, TRIM29 successfully reversed the resistance of HT29-OX resistant cell model to oxaliplatin. Conclusion. In mutant P53 colon cancer cell HT29, TRIM29 greatly increased the sensitivity of HT29 to oxaliplatin and reverse oxaliplatin resistance. The underlying mechanism is TRIM29 may increase the sensitivity of HT29 to oxaliplatin by blocking the transcriptional function of mutant P53, which inhibits the transcription function of its downstream gene such as MDR1. |
url |
http://dx.doi.org/10.1155/2021/8870907 |
work_keys_str_mv |
AT guoqionglei trim29reversesoxaliplatinresistanceofp53mutantcoloncancercell AT sushunliu trim29reversesoxaliplatinresistanceofp53mutantcoloncancercell AT xinyang trim29reversesoxaliplatinresistanceofp53mutantcoloncancercell AT chaohe trim29reversesoxaliplatinresistanceofp53mutantcoloncancercell |
_version_ |
1714694176152485888 |