01whole.pdf (3.21 MB)
Download file

The role of calcium channel drugs in lipopolysaccharide-induced oral cancer cell proliferation

Download (3.21 MB)
thesis
posted on 09.09.2022, 00:28 authored by Rajdeep ChakrabortyRajdeep Chakraborty

Introduction: Oral biofilms harbour Gram-negative and Gram-positive bacterial antigens—lipopolysaccharide (LPS) and lipoteichoic acid (LTA) respectively. LPS and alterations in calcium channels are known to influence oral cancer progression. Drugs that respectively activate or block these channels include the TRPV1 agonist capsaicin and ML218 HCl, a T-type voltage-gated calcium channel blocker. Hypothesis: Calcium channel drugs can reduce LPS-induced oral cancer cell proliferation. Method: Oral cancer cell lines SCC4, SCC9, SCC25 and CAL27, and the normal oral cell line OKF6 were used in this project. The level of calcium channel receptors expression was determined using qPCR. The effect on oral cancer cell proliferation of stimulation with LPS, LTA, ML218 HCl and capsaicin, either singly or in combination, was determined using MT Glo, trypan blue and clonogenic assays. RT-qPCR, phosphokinase array, western blot, TNF α ELISA and caspase-3/7 assays were employed to study proliferative and apoptotic pathways in bacterial antigen-stimulated oral cancer cells exposed to calcium channel drugs. Result: CAL27 showed higher Cav 3.3 (p ≤ 0.05), TRPV1 (by 20%) and lower Cav 3.1 (by 20%) expression than normal oral cells. Bacterial antigens stimulated CAL27 (p ≤ 0.001). CAL27 proliferation was lowest with treatment conditions involving ML218 HCl (p ≤ 0.001). Bacterial antigens and calcium channel drugs affected the expression of proliferation and tumour suppression factors (p ≤ 0.001). Conclusions: Bacterial antigens stimulate oral cancer cell proliferation, while calcium channel drugs reduce this effect. ML218 HCl may be a suitable drug for future treatment of oral cancer.

History

Table of Contents

1 Introduction -- 2 Cell lines and materials -- 3 Methods -- 4 Results -- 5 Discussion -- 6 Limitations of the study -- 7 Conclusion and future directions -- References -- Abbreviations -- Awards and journals -- Appendix

Notes

A thesis submitted in fulfillment of the requirements for the degree of Master of Research

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

Thesis (MRes), Macquarie University, Faculty of Medicine and Health Sciences, 2020

Department, Centre or School

Department of Biomedical Sciences

Year of Award

2020

Principal Supervisor

Karen Vickery

Rights

Copyright: The Author Copyright disclaimer: https://www.mq.edu.au/copyright-disclaimer

Language

Englsih

Extent

175 pages