PCR analysis of the effect of photodynamic therapy on breast tumors
DOI:
https://doi.org/10.33448/rsd-v10i12.20468Keywords:
Cancer; Gene expression; Photodynamic therapy.Abstract
Photodynamic therapy (PDT) is a promising therapeutic modality for treating cancer, including breast tumors. The oxidative damage caused by PDT culminates in cell death, induction of immune response, and the resulting destruction of the tumor. This study aimed to evaluate the gene expression profiling of genes BCL-2, BAX, and HER-2 and their proteins after PDT, associating it with the necrosis caused by this therapy under different fluences. Twenty-eight female rats received a single dose of 7,12-dimethylbenz (a) anthracene (DMBA - 80mg/kg), by gavage, for breast tumor induction. After the tumors grew, the animals were divided into four groups: G1 - control group – untreated breast tumor – and G2, G3, and G4 groups treated with PDT using Photogem@ as photosensitizer and interstitial irradiation, with fluences of 50J/cm, 100J/cm, and 150J/cm, respectively. Samples of tumors were harvested for histological examination by RT-qPCR. The RT-qPCR showed that the gene expression profiling of BCL-2, BAX, and HER-2 was not altered after PDT. Hemorrhagic necrosis and qualitatively greater vascular and cellular damage were observed and correlated positively with the fluence. PDT does not seem to induce the modulation of genes related to apoptosis. The results indicate that the type of cell death stimulated by PDT in breast tumor is necrosis.
References
Ahmed, A., Ali, A., Ali, S., Ahmad, A., Philip, P & Sarkar, F. (2012). Breast Cancer Metastasis and Drug Resistance, 1–18.
Alteri, R., Barnes, C., Burke, A., et al. (2013). American cancer society. Breast Cancer Facts & Figures, 2013-2014.
Appert-Collin, A. et al. (2015). Role of ErbB receptors in cancer cell migration and invasion. Frontiers in Pharmacology, 6, 1–10.
Barros, A. C. S. D., Muranaka, E. N. K., Mori, J. L., et al. (2004). Induction of experimental mammary carcinogenesis in rats with 7,12 Dimethylbenz(a)anthracene. Rev. Hosp. Clín. 59, 257-261.
Chiu, S. M., Xue, L.Y., Usuda, J., Azizuddin, K., & Oleinick, N. L. (2003). Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy. Brit. J. Cancer; 89, 1590-1597.
Diwu, Z., & Lown, J. W. (1990). Hypocrellins and their use in photosensitization. Photochem. Photobiol. 52, 609-616.
Duanmu, J. et al. (2011). Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy. British journal of cancer, 104, 9, 1401–1409.
Fang, Y., Tian, S., Pan, Y., Li, W., Wang, Q., Tang, Y., Yu, T., et al. (2020). Pyroptosis: A new frontier in cancer. Biomedicine & Pharmacotherapy, 121,1095952.
Ferreira, I., Ferreira, J., Vollet-Filho, J. D., et al. (2012). Photodynamic therapy for the treatment of induced mammary tumor in rats. Lasers Med. Sci. 28, 571-577. DOI 10.1007/s10103-012-1114-3.
George, B. P. A. & Abrahamse, H. (2016). A Review on Novel Breast Cancer Therapies Photodynamic Therapy. Anti-Cancer Agents in Medicinal Chemistry, 16, 793–801.
Graham, A., Li, G., Chen, Y. et al. (2003). Structure–activity relationship of new octaethylporphyrin-based benzochlorins as photosensitizers for photodynamic therapy. Photochem Photobiol, 77,561–566.
Halder, M., Chowdhury, P., Gordon, M., & Petrich, J. (2005). Hypericin and its perylene quinone analogs: probing structure, dynamics, and interactions with the environment. Adv. Photochem. 28. 10.1002/0471714127.ch1
Heffelfinger, S. C., Gear, R. B., Taylor, K. et al. (2000). DMBA-induced mammary pathologies are angiogenic in vivo and in vitro. Lab. Invest. 80, 485-92.
Hicks, D. G., & Kulkarni, S. (2008). HER2+ Breast Cancer: Review of Biologic Relevance and Optimal Use of Diagnostic Tools. Am. J. Clin. Pathol. 129, 263-273.
Itoh, M., Chiba, H., Noutomi, T., Takada, E. & Mizuguchi, J. (2000). Cleavage of Bax-alpha and Bcl-x (L) during carboplatin-mediated apoptosis in squamous cell carcinoma cell line. Oral Oncol. 36, 277-285.
Karim, B. O., Ali, S. Z., Landolfi, J. A., et al. (2008). Cytomorphologic differentiation of benign and malignant mammary tumors in fine needle aspirate specimens from irradiated female Sprague-Dawley rats. Vet. Clin. Pathol. 37, 229-236.
Kessel, D. & Arroyo, A. S. (2007). Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage. Photoch. Photobio. Sci. 6, 1290-1295.
Kocdor, H., Cehreli, R., Kocdor, M. A., Sis, B., Yilmaz, O., Canda, T., Demirkan, B., Resmi, H., Alakavuklar, M. & Harmancioglu, O. (2000). Toxicity induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene and the protective effects of selenium in Wistar rats. J. Toxicol. Env. Heal. A. 68, 693-701.
Koval, J., Mikes, J., Jendzelovsky, R., Kello, M., Solar, P. & Fedorocko, P. (2010). Degradation of HER2 Receptor Through Hypericin-mediated Photodynamic Therapy. Photochem Photobiol, 86, 200-205.
Livak, K. J. & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method. Methods. 25, 402-408.
Luo, Y. & Kessel, D. (1997). Initiation of apoptosis versus necrosis by photodynamic therapy with chloroaluminum phthalocyanine. Photochem Photobiol 66:479–483 20.
Martinez-Carpio, P. A. & Trelles, M. A. (2010). The role of epidermal growth factor receptor in photodynamic therapy: a review of the literature and proposal for future investigation. Lasers Med. Sci. 25, 767-771.
Najafov, A., Hongbo, C., & Yuan, J. (2017). Necroptosis and Cancer. Trends Cancer, 3, 4, 294–301. 10.1016/j.trecan.2017.03.002.
Oleinick, N. L.& Evans, H. H. (1998). The photobiology of photodynamic therapy: cellular targets and mechanisms. Radiat. Res.,150, 146-156.
Peng, Q., Moan, J & Nesland, J.M. (1996). Correlation of subcellular and intratumoral photosensitizer localization with ultrastructural features after photodynamic therapy. Ultrastruct Pathol, 20, 109–129.
Perlin, D. S., Murant, R. S., Gibson, S. L. & Hilf, R. (1985). Effects of Photosensitization by Hematoporphyrin Derivative on Mitochondria Adenosine Triphosphatase-mediated Proton Transport and Membrane Integrity of R3230AC Mammary Adenocarcinoma. Cancer Res. 45, 653-658.
Pitta, M. G. R., Silva, R. P. S. & Alves, G. V. S. (2021). Nanocarreadores aplicados ao tratamento do câncer de mama. Research, Society and Development, 10, 10, http://dx.doi.org/10.33448/rsd-v10i10.18966.
Russo, J & Russo, I. H. (1996). Experimentally induced mammary tumors in rats. Breast Cancer Res. Tr., 39, 7-20.
Russo, J. & Russo, I. H. (2000). Atlas and histologic classification of tumors of the rat mammary gland. J. Mammary Gland. Biol. 5, 187-200.
Russo, J., Russo, I. H., Rogers, A.E., Van Zwieten, M. J. & Gusterson, B. A. (1990) Tumors of the mammary gland. IARC Scientific Publications. 99, 47-78.
Senderowicz, A. M. (2004). Targeting cell cycle and apoptosis for the treatment of human malignancies. Curr. Opin. Cell. Biol. 16, 670-678.
Silva, J. C., Ferreira-Strixino, J., Fontana, L. C., Paula, L. M., Raniero, L., Martin A. A., Canevari, R. (2014). A. Apoptosis-associated genes related to photodynamic therapy in breast carcinomas. Lasers Med Sci, 29, 1429–1436.
Srivastava, M., Ahmad, N., Gupta, S. & Mukhtar, H. (2001). Involvement of Bcl-2 and Bax in photodynamic therapy-mediated apoptosis. Antisense Bcl-2 oligonucleotide sensitizes RIF 1 cells to photodynamic therapy apoptosis. J. Biol. Chem. 276, 15481-15488.
Ströbl, S., Domke, M., Rühm, A. & Srok, R. (2014). Investigation of non-uniformly emitting optical fiber diffusers on the light distribution in tissue. Biomedical Optics Express, 11, 7.
Teiten, M. H., Bezdetnaya, L., Morlière, P., Santus, R. & Guillemin, F. (2003). Endoplasmic reticulum and Golgi apparatus are de preferential sites of Foscan localization in cultured tumor cells. Brit J Cancer, 88, 1, 146-152.
Terada, S., Uchide, K., Suzuki, N., Akasofu, K. & Nishida, E. (1995). Induction of ductal carcinomas by intaductal administration of 7,12 dimethylbenz(a)anthracene in Wistar rats. Breast Cancer Res. Tr., 34, 35-43.
Usuda, J., Azizuddin, K., Chiu, S., & Oleinick, N. L. (2003). Association between the photodynamic loss of Bcl-2 and the sensitivity to apoptosis caused by phthalocyanine photodynamic therapy. Photochem. Photobiol. 78, 1-8.
Vohra N., Chavez, T., Troncoso, J. R., Rajaram, N., Wu, J., Coan P. N., Jackson, T. A., Bailey, K. & El-Shenawee M. (2021). Mammary tumors in Sprague Dawley rats induced by N-ethyl-N-nitrosourea for evaluating terahertz imaging of breast cancer. J. Med. Imag., 8, 2, https://doi.org/10.1117/1.JMI.8.2.023504
Wyld, L.; Reed, M. W. & Brown, N. J. (2001). Differential cell death response to photodynamic therapy is dependent on dose and cell type. British journal of cancer, 84, 10, p. 1384–1386.
Xue, L.Y., Chiu, S. M. & Oleinick, N. (2001). Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4. Oncogen. 20, 3420-3427.
Yeh, K. T., Chang, J. G., Lin, T. H., Wang, Y.F., Tien, N., Chang, J.Y., et al. (2003). Epigenetic changes of tumor suppressor genes, P15, P16, VHL and P53 in oral cancer. Oncol Rep, 10, 659–663.
Zheng, H. et al. (2019). Elevated serum HER-2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression. Cancer Medicine, 8, 2, 679–685.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Isabelle Ferreira; Glenda Nicioli da Silva; Juliana Ferreira-Strixino; Clovis Grecco; Vanderlei Salvador Bagnato; Daisy Maria Favero Salvadori; Juliana Guerra Pinto; Noeme Sousa Rocha
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
