Análise por PCR do efeito da terapia fotodinâmica em tumores mamários

Autores

DOI:

https://doi.org/10.33448/rsd-v10i12.20468

Palavras-chave:

Câncer; Expressão genética; Terapia fotodinâmica.

Resumo

A terapia fotodinâmica (TFD) é uma modalidade terapêutica promissora para o tratamento do câncer, incluindo tumores de mama. Os danos oxidativos causados pela TFD culminam na morte celular, indução da resposta imune e na consequente destruição do tumor. Este estudo teve como objetivo avaliar o perfil de expressão genética dos genes BCL-2, BAX e HER-2 e suas proteínas após o TFD, associando-o à necrose causada por essa terapia sob diferentes fluências. Vinte e oito ratas receberam uma única dose de 7,12 - dimetilbenzantraceno (DMBA - 80mg/kg), por gavage, para indução de tumor de mama. Após o crescimento dos tumores, os animais foram divididos em quatro grupos: G1 - grupo controle – tumor de mama não tratado – e grupos G2, G3 e G4 tratados com PDT usando Photogem@ como fotosensibilizante e irradiação intersticiais, com fluências de 50J/cm, 100J/cm e 150J/cm, respectivamente. Amostras de tumores foram colhidas para exame histológico por RT-qPCR. O RT-qPCR mostrou que o perfil de expressão genética de BCL-2, BAX e HER-2 não foi alterado após o TFD. Necrose hemorrágica e dano vascular e celular qualitativamente maior foram observados e correlacionados positivamente com a fluência. O TFD não parece induzir a modulação de genes relacionados à apoptose. Os resultados indicam que o tipo de morte celular estimulada pelo TFD no tumor mamário é a necrose.

Referências

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.

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Publicado

26/09/2021

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FERREIRA, I.; SILVA, G. N. da .; FERREIRA-STRIXINO, J.; GRECCO, C. .; BAGNATO, V. S. .; SALVADORI, D. M. F. .; PINTO, J. G. .; ROCHA, N. S. Análise por PCR do efeito da terapia fotodinâmica em tumores mamários. Research, Society and Development, [S. l.], v. 10, n. 12, p. e459101220468, 2021. DOI: 10.33448/rsd-v10i12.20468. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/20468. Acesso em: 2 jul. 2024.

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Ciências da Saúde