Collaborative role of calcitriol with buparlisib in the tongue squamous cell carcinoma cell line by modulating the Casp3 and Akt1 gene expression.

BACKGROUND

Oral squamous cell carcinoma (OSCC) is a devastating disease with an increasing incidence. Among the commonly dysregulated pathways in oncogenesis are the phosphatidylinositol 3-kinase / protein kinase-B/ mammalian target of rapamycin (PI3K/AKT/mTOR) and apoptotic pathways. Buparlisib, a pan-class I PI3K inhibitor, has antineoplastic effects, but its associated toxicities hinder its beneficial role in patients. Calcitriol, active vitamin D (Vit D), possesses anticancer functions by targeting both pathways. Therefore, Vit D could help achieve low buparlisib doses and boost its effects.

OBJECTIVES

The present study aimed to determine the effects of buparlisib and Vit D, separately and in co-administration, on cell viability, as well as the apoptotic and PI3K pathways in the human tongue squamous cell carcinoma (TSSC) HNO97 cell line.

MATERIAL AND

METHODS

The MTT assay was used to estimate the IC50 and the IC70 buparlisib doses, which were then co-administrated with 100 nmol and 1,000 nmol Vit D. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to evaluate the altered caspase-3 (Casp3) and Akt1 gene expressions after 48-hour treatment.

RESULTS

The co-administration of either 100 nmol or 1,000 nmol Vit D lowered the IC50 and the IC70 buparlisib doses. The qRT-PCR showed that for Casp3 expression, the 4 combination groups differed significantly from the IC50 and IC70 buparlisib doses. For Akt1 expression, the IC70 co-administration dose of buparlisib with 100 nmol Vit D, the IC50 co-administration dose of buparlisib with 1,000 nmol Vit D and the IC70 co-administration dose of buparlisib with 1,000 nmol Vit D were significantly different from the IC50 buparlisib dose. The IC70 buparlisib dose showed no significant alteration from the 4 combination groups.

CONCLUSIONS

Vitamin D represents an efficient anticancer adjuvant that permits a novel therapeutic strategy for cancer patients.