Determining the Effect of siRNA-Egr-1 and Camptothecin on Growth and Chemosensitivity of Breast Cancer Cells
Advanced Research in Biological Science Vol. 4,
25 September 2023
,
Page 95-110
https://doi.org/10.9734/bpi/arbs/v4/6236B
Abstract
In the present research, the breast cancer cell lines SK-BR3 and MCF-7 were used to explore the effects of a siRNA targeting the Egr-1, either alone or in conjunction with the breast cancer treatment camptothecin (Cpt), in reducing breast cancer cell survival and anchorage-independent growth.. Cancer is a global health problem responsible for one in six deaths worldwide. Treating cancer has been a highly complex process. Conventional treatment approaches, such as surgery, chemotherapy, and radiotherapy, have been in use, while significant advances are being made in recent times, including stem cell therapy, targeted therapy, ablation therapy, nanoparticles, natural antioxidants, radionics, chemodynamic therapy, sonodynamic therapy, and ferroptosis-based therapy. Current methods in oncology focus on the development of safe and efficient cancer nanomedicines. Low levels of Egr-1 expression have been found in mammary and lung cancers as well as the majority of normal tissues, raising the possibility that these low levels and the emergence of mammary neoplasias are related. However, investigations of the expression of Egr-1 in breast cancer cells, SK-BR3 and MCF-7, showed that these cells express endogenous Egr-1 at rather high levels. We used small interfering RNA (siRNA) against Egr-1 alone or in combination with Cpt to study the impact of blocking endogenous Egr-1 in breast cancer cells. We predicted that when the Egr-1 gene was blocked and treated with Cpt, the sensitivity of the cells to chemotherapeutic drugs would increase. Thus, we performed in vitro experiment to clarify the effect of Egr-1 on tumor cell lines growth. We made control and siRNA-Egr-1 using vector plasmids and then transfected SK-BR3 and MCF-7 cells. After treating the cells with siRNA-Egr-1, the cell lines were assayed with Cpt to confirm the effect of Egr-1 siRNA using the cell expression of mRNA and protein, proliferation assay and anchorage activity with soft agar. Human SK-BR3 and MCF-7 breast carcinoma cell growth and capacity of anchorage transfected with siRNA-Egr-1 or treated with Cpt was slower than that of the control group. This effect was increased when the cells were given simultaneously siRNA and camptothecin. The results strongly suggest that siRNA- Egr-1 alone or in combination with camptothecin could be a potent antineoplastic agent in suppressing the growth of breast tumor despite the known role of Egr-1 as a tumor- suppressor in several other types of human cancers.
- Breast carcinoma
- early growth response gene
- short RNA interference
- camptothecin