Rapamycin-Mediated mTOR Inhibition Reverses Drug Resistance to Adriamycin in Colon Cancer Cells.

Abstract

BACKGROUND/AIMS:

To detect the cellular sensitivity to adriamycin (ADR) by assessing autophagy, apoptosis, and multidrug resistance gene 1 (mdr1) expression in LoVo/Adr cells.

METHODOLOGY:

LoVo/Adr cells were designated accordingly into ADR group, Rapamycin (RAPA) group, ADR plus RAPA, and control group in main observations. Autophage, cell death and mdr1 were examined.

RESULTS:

IC50 value of ADR in LoVo/Adr was significantly decreased in response to RAPA (P < 0.05). Autophagy rate of LoVo/Adr cells was higher in the ADR or RAPA-alone group than in control (p < 0.05), while ADR/RAPA combination has significantly increased autophagy rate compared to ADR or RAPA alone (p < 0.05). Compared with controls, apoptosis rate in the RAPA group had no difference (p > 0.05); whereas there was significant difference in ADR group (p < 0.05). Furthermore, apoptosis rate was significantly different in combined RAPA/ADR compared to ADR (p < 0.05). Expression of mRNA and protein P-gp level of mdr 1 gene in LoVo/Adr cells were significantly decreased under RAPA-treated groups at 25 µmol/L and 50 µmol/L (p < 0.05).

CONCLUSION:

This study has indicated that the inhibition of the mTOR pathway reverses multidrug resistance in colorectal cancer cells, which is associated with increased autophagy, apoptosis and reduced mdr1 gene expression in drug-resistant cells treated with Adriamycin.

• Authors: Qiang Ma, Zonghong Chang, Wei Wang, Biaomeng Wang
• Journal: Hepato-gastroenterology (Hepatogastroenterology) Vol. 62 Issue 140 Pg. 880-6 (Jun 2015) ISSN: 0172-6390 [Print] Greece
• PMID: 26902021 (Publication Type: Journal Article)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• Antibiotics, Antineoplastic
• RNA, Messenger
• Doxorubicin
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics)
• Adenocarcinoma (genetics)
• Antibiotics, Antineoplastic (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Line, Tumor
• Colonic Neoplasms (genetics)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Humans
• RNA, Messenger (drug effects, metabolism)
• Sirolimus (pharmacology)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)