Ansari Mohammad Azam, Thiruvengadam Muthu, Farooqui Zeba, Rajakumar Govindaswamy, Sajid Jamal Qazi Mohammad, Alzohairy Mohammad A, Almatroudi Ahmad, Alomary Mohammad N, Chung Ill-Min, Al-Suhaimi Ebtesam Abdullah
Department of Epidemic Diseases Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441, Saudi Arabia.
Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul 05029, Republic of Korea.
Semin Cancer Biol. 2021 Feb;69:109-128. doi: 10.1016/j.semcancer.2019.12.022. Epub 2019 Dec 28.
Breast cancer is one of the most prevalent and reoccurring cancers and the second most common reason of death in women. Despite advancements in therapeutic strategies for breast cancer, early tumor recurrence and metastasis in patients indicate resistance to chemotherapeutic medicines, such as paclitaxel due to the abnormal expression of ER and EGF2 in breast cancer cells. Therefore, the development of alternatives to paclitaxel is urgently needed to overcome challenges involving drug resistance. An increasing number of studies has revealed miRNAs as novel natural alternative substances that play a crucial role in regulating several physiological processes and have a close, adverse association with several diseases, including breast cancer. Due to the therapeutic potential of miRNA and paclitaxel in cancer research, the current review focuses on the differential roles of various miRNAs in breast cancer development and treatment. miRNA delivery to a specific target site, the development of paclitaxel and miRNA formulations, and nanotechnological strategies for the delivery of nanopaclitaxel in the management of breast cancer are discussed. These strategies involve improving the cellular uptake and bioavailability and reducing the toxicity of free paclitaxel to achieve accumulation tumor site. Furthermore, a molecular docking study was performed to ascertain the enhanced anticancer activity of the nanoformulation of ANG1005 and Abraxane. An in silico analysis revealed that ANG1005 and Abraxane nanoformulations have superior and significantly enhanced interactions with the proteins α-tubulin and Bcl-2. Therefore, ANG1005 and Abraxane may be more suitable in the therapeutic management of breast cancer than the existing free paclitaxel. miRNAs can revert abnormal gene expression to normalcy; since miRNAs serve as tumor suppressors. Therefore, restoration of particular miRNAs levels as a replacement therapy may be an effective endocrine potential strategy for treating ER positive/ negative breast cancers.
乳腺癌是最常见且易复发的癌症之一，也是女性第二大常见死因。尽管乳腺癌治疗策略取得了进展，但患者早期肿瘤复发和转移表明对化疗药物存在耐药性，例如由于乳腺癌细胞中ER和EGF2的异常表达而对紫杉醇耐药。因此，迫切需要开发替代紫杉醇的药物来克服耐药性带来的挑战。越来越多的研究表明，微小RNA（miRNA）是新型天然替代物质，在调节多种生理过程中起关键作用，并且与包括乳腺癌在内的多种疾病存在密切的不良关联。由于miRNA和紫杉醇在癌症研究中的治疗潜力，本综述重点关注各种miRNA在乳腺癌发生和治疗中的不同作用。讨论了将miRNA递送至特定靶位点、紫杉醇和miRNA制剂的开发以及纳米技术策略在乳腺癌治疗中递送纳米紫杉醇的应用。这些策略包括提高细胞摄取和生物利用度以及降低游离紫杉醇的毒性，以实现肿瘤部位的药物蓄积。此外，进行了分子对接研究以确定ANG1005和白蛋白结合型紫杉醇纳米制剂增强的抗癌活性。计算机模拟分析表明，ANG1005和白蛋白结合型紫杉醇纳米制剂与α-微管蛋白和Bcl-2蛋白具有更强且显著增强的相互作用。因此，ANG1005和白蛋白结合型紫杉醇在乳腺癌治疗管理中可能比现有的游离紫杉醇更合适。miRNA可将异常基因表达恢复正常；因为miRNA起着肿瘤抑制作用。因此，可以将恢复特定miRNA水平作为替代疗法，这可能是治疗雌激素受体阳性/阴性乳腺癌的一种有效的内分泌潜在策略。
