MiR-138 Suppresses the PDK1 Expression to Decrease the Oxaliplatin Resistance of Colorectal Cancer.
PDK1
colorectal cancer
miR-138
oxaliplatin
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
12
2019
accepted:
29
03
2020
entrez:
21
5
2020
pubmed:
21
5
2020
medline:
21
5
2020
Statut:
epublish
Résumé
Oxaliplatin is one kind of platinum-based drug. It is effective and commonly used in the treatment of colorectal cancer (CRC). However, development of acquired drug resistance is still a big obstacle during the oxaliplatin therapy. It is urgent to take strategies to decrease the oxaliplatin resistance of CRC. Oxaliplatin-resistant HT29 and SW480 (HT29/R and SW480/R) cells were acquired through long-term exposure to oxaliplatin by using the routine HT29 and SW480 cells. Relative glucose consumption, lactate generation and LDH activity were tested to evaluate the glycolysis of CRC cell lines. MTT assays were conducted to evaluate the differences of oxaliplatin sensitivity between HT29/R (SW480/R) cells and their parental HT29 (SW480) cells. Regulation of miR-138 on PDK1 was confirmed through qRT-PCR, Western blot and dual-luciferase reporter assays. Reactive oxygen species (ROS) levels were measured by flow cytometry. HT29/R and SW480/R cells exhibited higher glucose consumption, lactate production and LDH activity compared to their parental HT29 and SW480 cells. However, oxygen consumption rate (OCR) in HT29/R and SW480/R cells is lower than that in HT29 and SW480 cells, respectively. Results of MTT assays showed that treatment with miR-138 can increase the cytotoxicity of oxaliplatin to HT29/R and SW480/R cells. Research on mechanisms showed that PDK1 was the target of miR-138. Overexpression of miR-138 can inhibit the expression of PDK1, and thus increase the OCR of HT29/R and SW480/R cells. Under the treatment of oxaliplatin, the miR-138-overexpressed HT29/R and SW480/R cells generated more amount of ROS to get into the apoptosis process. Overexpression of miR-138 suppressed the PDK1 expression to decrease the oxaliplatin resistance of CRC.
Sections du résumé
BACKGROUND
BACKGROUND
Oxaliplatin is one kind of platinum-based drug. It is effective and commonly used in the treatment of colorectal cancer (CRC). However, development of acquired drug resistance is still a big obstacle during the oxaliplatin therapy. It is urgent to take strategies to decrease the oxaliplatin resistance of CRC.
MATERIALS AND METHODS
METHODS
Oxaliplatin-resistant HT29 and SW480 (HT29/R and SW480/R) cells were acquired through long-term exposure to oxaliplatin by using the routine HT29 and SW480 cells. Relative glucose consumption, lactate generation and LDH activity were tested to evaluate the glycolysis of CRC cell lines. MTT assays were conducted to evaluate the differences of oxaliplatin sensitivity between HT29/R (SW480/R) cells and their parental HT29 (SW480) cells. Regulation of miR-138 on PDK1 was confirmed through qRT-PCR, Western blot and dual-luciferase reporter assays. Reactive oxygen species (ROS) levels were measured by flow cytometry.
RESULTS
RESULTS
HT29/R and SW480/R cells exhibited higher glucose consumption, lactate production and LDH activity compared to their parental HT29 and SW480 cells. However, oxygen consumption rate (OCR) in HT29/R and SW480/R cells is lower than that in HT29 and SW480 cells, respectively. Results of MTT assays showed that treatment with miR-138 can increase the cytotoxicity of oxaliplatin to HT29/R and SW480/R cells. Research on mechanisms showed that PDK1 was the target of miR-138. Overexpression of miR-138 can inhibit the expression of PDK1, and thus increase the OCR of HT29/R and SW480/R cells. Under the treatment of oxaliplatin, the miR-138-overexpressed HT29/R and SW480/R cells generated more amount of ROS to get into the apoptosis process.
CONCLUSION
CONCLUSIONS
Overexpression of miR-138 suppressed the PDK1 expression to decrease the oxaliplatin resistance of CRC.
Identifiants
pubmed: 32431512
doi: 10.2147/OTT.S242929
pii: 242929
pmc: PMC7198439
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3607-3618Informations de copyright
© 2020 Wang et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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