Dental and medical problems · 2025
Collaborative role of calcitriol with buparlisib in the tongue squamous cell carcinoma cell line by modulating the Casp3 and Akt1 gene expression.
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Shamaa Karma Nabeel, Ahmed Basma Abdelrahman, Helmy Iman Mohamed
Аннотация
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.
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.