Analysis of TGF-β Gene Expression in Carboplatin Treated Lung Cancer Cells
Abstract:
Cancer, characterized by uncontrolled cell growth,
remains a formidable challenge in modern medicine. Among various treatment
modalities, chemotherapy, a systemic approach using drugs to impede cancer cell
proliferation, is a cornerstone of cancer therapy. This study aimed to analyze
the trends in TGF-β gene expression in carboplatin-treated lung cancer cell
line A549. The materials and methods included an MTT assay to assess cell
survivability, RNA isolation using the TRIzol method, and further analysis by
RT-PCR, with data statistically analyzed using SPSS software. Results showed
that TGF-β gene expression was significantly lower in the A549 cell line
treated with carboplatin compared to the untreated cell line. Specifically, the
treated cells exhibited a 40% reduction in TGF-β expression, a statistically
significant decrease (p < 0.05). Given that TGF-β is known to promote tumorigenesis,
the observed reduction suggests that carboplatin may control tumor progression by
downregulating TGF- β expression and the proliferation of cancer cells. In
conclusion, our study demonstrates the effectiveness of carboplatin as a
chemotherapy agent in inhibiting the proliferation of lung cancer cells (A549)
in non-small cell lung cancer (NSCLC) by reducing TGF-β gene expression levels.
These findings underscore the potential of carboplatin to modulate gene
expression associated with tumor growth, offering a promising therapeutic
strategy for NSCLC management. Future studies should explore the broader
implications of TGF-β modulation in cancer treatment and investigate the
potential of combining carboplatin with other therapeutic agents to enhance its
efficacy.
References:
[1]. Siegel, R. L., Giaquinto, A. N., & Jemal,
A., (2024). Cancer statistics, 2024. CA: A Cancer Journal for Clinicians,
74(1), 12–49. https://doi.org/10.3322/caac.21820
[2].
World
Health Organization., (2023, May). Lung Cancer. Https://Www.Who.Int/News-Room/Fact-Sheets/Detail/Lung-Cancer
[3].
Chaitanya
Thandra, K., Barsouk, A., Saginala, K., Sukumar Aluru, J., & Barsouk, A.,
(2021). Epidemiology of lung cancer. Współczesna Onkologia, 25(1),
45–52. https://doi.org/10.5114/wo.2021.103829
[4].
Alexander,
M., Kim, S. Y., & Cheng, H., (2020). Update 2020: Management of Non-Small
Cell Lung Cancer. Lung, 198(6), 897–907. https://doi.org/10.1007/s00408-020-00407-5
[5].
Couraud,
S., Zalcman, G., Milleron, B., Morin, F., & Souquet, P.-J., (2012). Lung
cancer in never smokers – A review. European Journal of Cancer, 48(9),
1299–1311. https://doi.org/10.1016/j.ejca.2012.03.007
[6].
Zhang,
C., Xu, C., Gao, X., & Yao, Q., (2022). Platinum-based drugs for cancer
therapy and anti-tumor strategies. Theranostics, 12(5),
2115–2132. https://doi.org/10.7150/thno.69424
[7].
Sun,
C.-C., Li, S.-J., & Li, D.-J. (2016). Hsa-miR-134 suppresses non-small cell
lung cancer (NSCLC) development through down-regulation of CCND1. Oncotarget,
7(24), 35960–35978. https://doi.org/10.18632/oncotarget.8482
[8].
Liu,
X., Han, Q., Rong, X., Yang, M., Han, Y., Yu, J., & Lin, X., (2020). ANKHD1
promotes the proliferation and invasion of non-small‑cell lung cancer cells via
regulating YAP oncoprotein expression and inactivating the Hippo pathway. International
Journal of Oncology. https://doi.org/10.3892/ijo.2020.4994
[9].
Kuppusamy,
K. M., Selvaraj, S., Singaravelu, P., John, C. M., Racheal, K., Varghese, K.,
Kaliyamoorthy, D., Perumal, E., & Gunasekaran, K., (2023). Anti-microbial
and anti-cancer efficacy of acetone extract of Rosa chinensis against resistant
strain and lung cancer cell line. BMC Complementary Medicine and Therapies,
23(1), 406. https://doi.org/10.1186/s12906-023-04222-2
[10]. Ganesh, A., Ashikha Shirin Usman, P. P., K. P., A., Thomas, P., Ganapathy, D. M., &
Sekar, D., (2024). Expression analysis of transforming growth factor beta
(TGF-β) in oral squamous cell carcinoma. Oral Oncology Reports, 9,
100195. https://doi.org/10.1016/j.oor.2024.100195
[11]. Villar, V. H., Subotički, T., Đikić, D.,
Mitrović-Ajtić, O., Simon, F., & Santibanez, J. F. (2023). Transforming
Growth Factor-β1 in Cancer Immunology: Opportunities for Immunotherapy (pp.
309–328). https://doi.org/10.1007/978-3-031-26163-3_17
[12]. Lamouille, S., Xu, J., & Derynck, R.
(2014). Molecular mechanisms of epithelial-mesenchymal transition. Nature
Reviews. Molecular Cell Biology, 15(3), 178–196. https://doi.org/10.1038/nrm3758
[13]. van den Bulk, J., de Miranda, N. F. C. C.,
& ten Dijke, P., (2021). Therapeutic targeting of TGF-β in cancer: hacking
a master switch of immune suppression. Clinical Science, 135(1), 35–52. https://doi.org/10.1042/CS20201236
[14]. Dasari, S., & Tchounwou, P. B., (2014).
Cisplatin in cancer therapy: molecular mechanisms of action. European
Journal of Pharmacology, 740, 364–378. https://doi.org/10.1016/j.ejphar.2014.07.025
[15]. National Cancer Institute., (2007). Carboplatin.
National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/drugs/carboplatin
[16]. Stöhr, W., Paulides, M., Bielack, S.,
Jürgens, H., Koscielniak, E., Rossi, R., Langer, T., & Beck, J. D., (2007).
Nephrotoxicity of cisplatin and carboplatin in sarcoma patients: A report from
the late effects surveillance system. Pediatric Blood & Cancer, 48(2),
140–147. https://doi.org/10.1002/pbc.20812
[17]. Rajasegaran, T., How, C. W., Saud, A., Ali,
A., & Lim, J. C. W., (2023). Targeting Inflammation in Non-Small Cell Lung
Cancer through Drug Repurposing. Pharmaceuticals, 16(3), 451. https://doi.org/10.3390/ph16030451
[18]. Cocetta, V., Ragazzi, E., & Montopoli, M.,
(2019). Mitochondrial Involvement in Cisplatin Resistance. International
Journal of Molecular Sciences, 20(14), 3384. https://doi.org/10.3390/ijms20143384
[19]. Galluzzi, L., Senovilla, L., Vitale, I.,
Michels, J., Martins, I., Kepp, O., Castedo, M., & Kroemer, G., (2012).
Molecular mechanisms of cisplatin resistance. Oncogene, 31(15),
1869–1883. https://doi.org/10.1038/onc.2011.384
[20]. Kogure, Y., Iwasawa, S., Saka, H., Hamamoto,
Y., Kada, A., Hashimoto, H., Atagi, S., Takiguchi, Y., Ebi, N., Inoue, A.,
Kurata, T., Okamoto, I., Yamaguchi, M., Harada, T., Seike, M., Ando, M., Saito,
A. M., Kubota, K., Takenoyama, M., Gemma,
A. (2021). Efficacy and safety of carboplatin with nab-paclitaxel versus
docetaxel in older patients with squamous non-small-cell lung cancer (CAPITAL):
A randomised, multicentre, open-label, phase 3
trial. The Lancet Healthy Longevity, 2(12), e791–e800. https://doi.org/10.1016/S2666-7568(21)00255-5
[21]. Shreya Reddy, C. S., Usman P. P, A. S., Ganapathy, D. M., K. P., A., & Sekar, D., (2024). MicroRNA-21
as a biomarker in terminal stage oral squamous cell carcinoma (OSCC) in the
South Indian population. Oral Oncology Reports, 9, 100139. https://doi.org/10.1016/j.oor.2023.100139
[22]. Preca, B.-T., Bajdak, K., Mock, K., Lehmann,
W., Sundararajan, V., Bronsert, P., Matzge-Ogi, A., Orian-Rousseau, V.,
Brabletz, S., Brabletz, T., Maurer, J., & Stemmler, M. P. (2017). A novel
ZEB1/HAS2 positive feedback loop promotes EMT in breast cancer. Oncotarget,
8(7), 11530–11543. https://doi.org/10.18632/oncotarget.14563
[23]. Deng, R., Wang, S.-M., Yin, T., Ye, T.-H.,
Shen, G.-B., Li, L., Zhao, J.-Y., Sang, Y.-X., Duan, X.-G., & Wei, Y.-Q.,
(2012). Inhibition of Tumor Growth and Alteration of Associated Macrophage Cell
Type by an HO-1 Inhibitor in Breast Carcinoma-Bearing Mice. Oncology
Research Featuring Preclinical and Clinical Cancer Therapeutics, 20(10),
473–482. https://doi.org/10.3727/096504013X13715991125684
