Breast cancer is one of the most frequent cancers among women worldwide. However, there is still no effective therapeutic strategy for advanced breast cancer that has metastasized. Aberrant activation of the PI3K/AKT/mTOR pathway is an essential step for the growth of human breast cancers. In our previous study, we designed and synthesized DHW-208 (2,4-difluoro-N-(5-(4-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)quinazolin-6-yl)-2-methoxypyridin-3-yl)benzenesulfonamide) as a novel pan-PI3K inhibitor. This study aimed to assess the therapeutic efficacy of DHW-208 in breast cancer and investigate its underlying mechanism. We found that DHW-208 inhibited the growth, proliferation, migration, and invasion of breast cancer cells. Moreover, DHW-208 induced breast cancer cell apoptosis via the mitochondrial pathway and induced G0/G1 cell-cycle arrest. In vitro results show that DHW-208 is a dual inhibitor of PI3K and mTOR, and suppress the growth of human breast cancer cells by targeting the PI3K/AKT/mTOR pathway. Consistent with the in vitro results, in vivo studies demonstrated that DHW-208 elicits an antitumor effect by inhibiting the PI3K/AKT/mTOR-signaling pathway with a high degree of safety in breast cancer. Above all, we report for the first time that DHW-208 suppressed the growth of human breast cancer cells by inhibiting the PI3K/AKT/mTOR-signaling pathway both in vivo and in vitro. Our study may provide evidence for the use of DHW-208 as an effective, novel therapeutic candidate for the treatment of human breast cancers in clinical trials.

乳腺癌是全世界女性中最常见的癌症之一。然而，对于转移的晚期乳腺癌仍然没有有效的治疗策略。PI3K / AKT / mTOR途径的异常激活是人类乳腺癌生长的重要步骤。在先前的研究中，我们设计并合成了DHW-208（2,4-difluoro-N-（5-（4-（（1-（2-hydroxyethyl）-1H-pyrazol-4-yl）amino）quinazolin-6 -yl）-2-甲氧基吡啶-3--3-基）苯磺酰胺）作为新型泛PI3K抑制剂。这项研究旨在评估DHW-208在乳腺癌中的治疗效果并研究其潜在机制。我们发现DHW-208抑制乳腺癌细胞的生长，增殖，迁移和侵袭。此外，DHW-208通过线粒体途径诱导乳腺癌细胞凋亡，并诱导G0 / G1细胞周期停滞。体外结果表明，DHW-208是PI3K和mTOR的双重抑制剂，并通过靶向PI3K / AKT / mTOR途径抑制人乳腺癌细胞的生长。与体外结果一致，体内研究表明，DHW-208通过抑制PI3K / AKT / mTOR信号通路而在乳腺癌中具有高度的安全性，从而具有抗肿瘤作用。最重要的是，我们首次报道DHW-208通过在体内和体外抑制PI3K / AKT / mTOR信号通路来抑制人乳腺癌细胞的生长。我们的研究可能为在临床试验中使用DHW-208作为有效，新颖的治疗人乳腺癌的候选药物提供证据。通过靶向PI3K / AKT / mTOR途径来抑制人乳腺癌细胞的生长。与体外结果一致，体内研究表明，DHW-208通过抑制PI3K / AKT / mTOR信号通路而在乳腺癌中具有高度的安全性，从而具有抗肿瘤作用。最重要的是，我们首次报道DHW-208通过在体内和体外抑制PI3K / AKT / mTOR信号通路来抑制人乳腺癌细胞的生长。我们的研究可能为在临床试验中将DHW-208用作治疗人类乳腺癌的有效，新颖的治疗手段提供证据。通过靶向PI3K / AKT / mTOR途径来抑制人乳腺癌细胞的生长。与体外结果一致，体内研究表明，DHW-208通过抑制PI3K / AKT / mTOR信号通路而在乳腺癌中具有高度的安全性，从而具有抗肿瘤作用。最重要的是，我们首次报道DHW-208通过在体内和体外抑制PI3K / AKT / mTOR信号通路来抑制人乳腺癌细胞的生长。我们的研究可能为在临床试验中将DHW-208用作治疗人类乳腺癌的有效，新颖的治疗手段提供证据。最重要的是，我们首次报道DHW-208通过在体内和体外抑制PI3K / AKT / mTOR信号通路来抑制人乳腺癌细胞的生长。我们的研究可能为在临床试验中将DHW-208用作治疗人类乳腺癌的有效，新颖的治疗手段提供证据。最重要的是，我们首次报道DHW-208通过在体内和体外抑制PI3K / AKT / mTOR信号通路来抑制人乳腺癌细胞的生长。我们的研究可能为在临床试验中将DHW-208用作治疗人类乳腺癌的有效，新颖的治疗手段提供证据。