Effects of Ruxolitinib and Calcitriol Combination Treatment on Various Molecular Subtypes of Breast Cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Previous studies reported individual anticancer effects of ruxolitinib and calcitriol against breast cancer.
• The combined effect of ruxolitinib and calcitriol on diverse breast cancer molecular subtypes remains uninvestigated.

Purpose of the Study:

• To explore the synergistic anticancer potential of combining ruxolitinib and calcitriol across different breast cancer molecular subtypes.
• To evaluate the in vitro and in vivo effects of this combination on cell proliferation, apoptosis, cell cycle, and signaling pathways.

Main Methods:

• Utilized breast cancer cell lines (MCF-7, SKBR3, MDA-MB-468) for in vitro studies.
• Assessed cell proliferation, apoptosis, cell cycle progression, and key protein markers.
• Conducted in vivo studies using a MDA-MB-468 xenograft mouse model to confirm antitumor effects and assess toxicity.

Main Results:

• Demonstrated synergistic anticancer activity of the ruxolitinib-calcitriol combination in SKBR3 (HER2-enriched) and MDA-MB-468 (triple-negative) cells, but not MCF-7 (luminal) cells.
• Observed inhibition of proliferation, induction of apoptosis, cell cycle arrest, and modulation of related signaling proteins (cyclin D1, CDK1, CDK4, p21, p27, c-caspase, c-PARP, c-Myc, p-p53, p-JAK2).
• Confirmed synergistic antitumor efficacy in vivo in the MDA-MB-468 xenograft model with alterations in c-PARP, cyclin D1, and c-Myc expression, and no significant drug toxicity.

Conclusions:

• The combination of ruxolitinib and calcitriol exhibits a synergistic anticancer effect, particularly in HER2-enriched and triple-negative breast cancer subtypes.
• Treatment efficacy is dependent on the molecular subtype of breast cancer, highlighting the need for personalized therapeutic strategies.
• This combination warrants further investigation as a potential targeted therapy for specific breast cancer subtypes.