OVEREXPRESSION OF CYCLIN D1 IN ORAL CANCER INCREASES TPF CHEMOTHERAPEUTIC DRUGS VIA ACTIVATING THE CASPASE-3 PATHWAY

A GEORGE; . SIDRAH; A ALI; M ZAMAN; R AKHTAR; Y MEMON; K AAMIR; A RAMZAN

doi:10.54112/bcsrj.v2023i1.604

Authors

A GEORGE Department of Pathology, Dow Ojha Campus, Karachi, Pakistan
. SIDRAH Department of Pathology, Bilawal Medical College For Boys, Liaquat University of Medical and Health Sciences Jamshoro, Hyderabad, Pakistan
A ALI Department of Pathology, Jhalwan Medical College Khuzdar, Balochistan, Pakistan
M ZAMAN Department of Pathology, Liaquat University of Medical and Health Sciences Jamshoro, Hyderabad, Pakistan
R AKHTAR Department of Pathology, Liaquat University of Medical and Health Sciences Jamshoro, Hyderabad, Pakistan
Y MEMON Department of Dental Surgery, Liaquat University of Medical and Health Sciences Jamshoro, Hyderabad/ Dental Surgeon Bhittai Hospital Latifabad, Hyderabad. Pakistan
K AAMIR Department of Pathology, Liaquat University of Medical and Health Sciences Jamshoro, Hyderabad, Pakistan
A RAMZAN Department of Pathology, Liaquat University of Medical and Health Sciences Jamshoro, Hyderabad, Pakistan

DOI:

https://doi.org/10.54112/bcsrj.v2023i1.604

Keywords:

Oral Cancer, Caspase3 Pathway, Cyclin D1 Overexpression, Chemosensitivity, TPF Chemotherapeutic Agents

Abstract

Previous studies have indicated that induction chemotherapy can limit the possibility of early lesion eradication and lessen the severity of globally advanced tumors. This study aimed to ascertain if cyclin D1 expression in OSCC patients who were qualified for TPF induction chemotherapy might be regarded as a valid prognostic indicator for long-term outcomes. This study aimed to determine whether or not there was a connection between OSCC cell intervention and the production of cyclin D1 and chemosensitivity to TPF medicines through the apoptotic mechanism. The current work used immunohistochemistry to determine the expression of cyclin D1 in various tissues. To ascertain the survival rate of 232 people diagnosed with locally advanced oral squamous cell carcinoma (OSCC), the study utilized the log-rank test and Kaplan-Meier analysis. The participants in this historical clinical trial were observed for a mean duration of five years. Cytotoxicity assays were employed to assess the therapeutic effectiveness of TPF chemotherapy drugs. The activity of caspase-3 and PARP was evaluated in the HB96, CAL27, and HN30 cell lines following cyclin D1 inhibition, respectively. Long-term clinical outcomes were significantly better for patients with OSCC whose cancer cells expressed low amounts of cyclin D1 than those whose cells expressed high protein levels. Time to initial illness occurrence, time to initial local recurrence, time to mortality, and overall survival were among the metrics evaluated. The groups with low and high expression levels of cyclin D1 showed significantly different survival rates for disease-free survival, overall survival (OS), DMFS, local recurrence-free survival, and local recurrence-free survival (p0.001, 0.003, 0.004, and 0.001, respectively). Patients with cN2 oral squamous cell carcinoma (OSCC) with higher cyclin D1 expression had better distant metastasis-free survival (OS, P=0.024; DMFS, P=0.024) and overall survival (OS, P=0.024; DMFS, P=0.024) with TPF induction chemotherapy. However, patients with cN2 OSCC and low cyclin D1 expression did not show this survival advantage (P=0.024). Research has shown that oral squamous cell carcinoma (OSCC) is more sensitive to TPF-based chemotherapeutic drugs using caspase-3-mediated apoptosis that occurs when cyclin D1 expression rises. Based on these results, TPF induction chemotherapy may provide longer-term benefits than traditional treatment approaches for patients with cN2 OSCC and high cyclin D1 expression. Through a caspase-3-dependent mechanism, oral squamous cell carcinoma (OSCC) cell lines become more susceptible to TPF chemotherapeutic drugs when cyclin D1 is overexpressed.

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