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Chia seeds oil suppresses the resistance of hepatocellular carcinoma cells to liposomal-doxorubicin and upregulates the tumor suppressor miRNAs.

BACKGROUND
Chia seed is an oil-seed of multiple biological activities. Doxorubicin is an effective chemotherapy for liver cancer. Resistance and adverse effects are doxorubicin limitations.


OBJECTIVE
This study aimed to investigate the effect of chia seeds oil (CSO) on the resistance of HepG2 cells to liposomal-doxorubicin (DOX).


METHODS
The objective were investigated through measuring cytotoxicity, doxorubicin-metabolizing enzyme Cytochrome P450 3A4 (CYP-3A4), multidrug resistance-associated protein (MRP1), and the expression of multiple tumor suppressor microRNAs.


RESULTS
The findings indicated that low concentration of CSO increased HepG2 cells sensitivity to DOX as concluded from its higher cytotoxicity. DOX induced mRNAs of CYP-3A4 and MRP1 and their protein levels. CSO inhibited both in DOX-treated cells. CSO induced tumor suppressor miRNAs. Doxorubicin inhibited miR-122 and let-7/b/e expression, while it led to overexpression of let-7a. CSO/DOX upregulated let-7/b/e, miR-34a, and miR-122 (which inhibits MRP1) and downregulated let-7a that may lead to increased apoptosis.


CONCLUSION
CSO effectively re-sensitized HepG2 cells to liposomal-doxorubicin via inhibiting MRP1 and CYP-3A4 that may increase in vivo doxorubicin bioavailability and decrease its therapeutic dose to diminish its adverse effects.