January 1, 2023Open Access

Oleic acid-induced metastasis of KRAS/p53-mutant colorectal cancer relies on concurrent KRAS activation and IL-8 expression bypassing EGFR activation

Key Result

Antioxidants, statins, and IL-8 targeting may improve outcomes in metastatic colorectal cancer harboring multigene mutations and anti-EGFR resistance.

Structured PICO

Does oleic acid induce metastasis in KRAS/p53-mutant colorectal cancer via the ANGPTL4/IL-8/NOX4 axis, and can statins or antioxidants prevent it?

Population

Preclinical models including human colorectal cancer cell lines (HCT116, SW480, SW620, DLD-1, HT-29, Caco2, Colo320dm), 6-week-old male severe combined immunodeficiency (SCID) mice, 23 paired clinical CRC tissues, and TCGA database cohort (n=597).

Intervention

Oleic acid (OA) treatment, high-fat diet (HFD), statins (atorvastatin), vitamin E, reparixin, and genetic knockdowns (siRNA for KRAS, IL-8, ANGPTL4).

Comparator

Control conditions (vehicle treatment, scrambled siRNA, normal diet).

Outcome

Tumor metastasis (lung extravasation and pulmonary metastatic nodules), ROS production, and expression of IL-8, ANGPTL4, and NOX4.surrogate

Oleic acid promotes metastasis in KRAS/p53-mutant colorectal cancer through the ANGPTL4/IL-8/NOX4 pathway, which can be attenuated by statins and antioxidants.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

The antioxidants, statins, and targeting IL-8 may provide better outcomes for treating metastatic CRC that harbors multigene mutations and anti-EGFR resistance.

اسأل الذكاء الاصطناعي

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