乳腺癌是一种全球威胁女性生命的致命疾病，需要有效的治疗。选择性和安全地靶向癌细胞治疗似乎是最佳选择，因为大多数化疗药物作用的非选择性。罂粟碱通过扩张血管获得的高安全性和增加血流显示出有希望的抗肿瘤活性。同时，人们广泛注意到使用新城疫病毒进行病毒疗法对广泛范围的癌细胞安全和选择性有效。此外，联合治疗是有利的，因为它通过多种机制攻击癌细胞并增强病毒进入肿瘤块，克服了癌细胞对治疗的抵抗。因此，我们的目标是评估新城疫病毒的AMHA1菌株（NDV）和非麻醉类罂粟生物碱（罂粟碱）对乳腺癌模型的体外和体内组合治疗的效果。方法。体外实验使用两种人类乳腺癌细胞系和一种正常细胞系，分别进行了NDV、罂粟碱和联合治疗。研究包括细胞存活的MTT测定、形态学分析和凋亡检测。动物实验使用AN3小鼠乳腺腺癌肿瘤模型。抗肿瘤活性的评价包括生长抑制测量；免疫组化检测测量Caspase蛋白的表达。最后，采用半定量的微阵列分析检测凋亡相关蛋白的变化。体外结果显示，联合治疗对癌细胞产生协同细胞毒作用和凋亡，而对正常细胞的细胞毒作用微乎其微。体内，联合治疗诱导显著的抗肿瘤效应，肿瘤大小明显减小，与单独治疗相比，Caspase-3、Caspase-8和Caspase-9的表达显著和明显增加。微阵列分析表明，联合治疗组的凋亡相关蛋白水平较高。综上所述，本研究证明了罂粟碱在增强NDV抗肿瘤活性中的作用，为通过非化疗药物进行乳腺癌治疗提供了有希望的策略。版权所有©2023 Sura Akram等。

Breast cancer is a lethal disease in females worldwide and needs effective treatment. Targeting cancer cells with selective and safe treatment seems like the best choice, as most chemotherapeutic drugs act unselectively. Papaverine showed promising antitumor activity with a high safety profile and increased blood flow through vasodilation. At the same time, it was widely noticed that virotherapy using the Newcastle disease virus proved to be safe and selective against a broad range of cancer cells. Furthermore, combination therapy is favorable, as it attacks cancer cells with multiple mechanisms and enhances virus entrance into the tumor mass, overcoming cancer cells' resistance to therapy. Therefore, we aimed at assessing the novel combination of the AMHA1 strain of Newcastle disease virus (NDV) and nonnarcotic opium alkaloid (papaverine) against breast cancer models in vitro and in vivo. Methods. In vitro experiments used two human breast cancer cell lines and one normal cell line and were treated with NDV, papaverine, and a combination. The study included a cell viability MTT assay, morphological analysis, and apoptosis detection. Animal experiments used the AN3 mouse mammary adenocarcinoma tumor model. Evaluation of the antitumor activity included growth inhibition measurement; the immunohistochemistry assay measured caspase protein expression. Finally, a semiquantitative microarray assay was used to screen changes in apoptotic proteins. In vitro, results showed that the combination therapy induces synergistic cytotoxicity and apoptosis against cancer cells with a negligible cytotoxic effect on normal cells. In vivo, combination treatment induced a significant antitumor effect with an obvious regression in tumor size and a remarkable and significant expression of caspase-3, caspase-8, and caspase-9 compared to monotherapies. Microarray analysis shows higher apoptosis protein levels in the combination therapy group. In conclusion, this study demonstrated the role of papaverine in enhancing the antitumor activity of NDV, suggesting a promising strategy for breast cancer therapy through nonchemotherapeutic drugs.Copyright © 2023 Sura Akram et al.