Current pharmacological therapies and treatments targeting pancreatic neuroendocrine tumors (PNETs) have proven ineffective, far too often. Therefore, there is an urgent need for alternative therapeutic approaches. Zyflamend, a combination of anti-inflammatory herbal extracts, that has proven to be effective in various in vitro and in vivo cancer platforms, shows promise. However, its effects on pancreatic cancer, in particular, remain largely unexplored. In the current study, we investigated the effects of Zyflamend on the survival of beta-TC-6 pancreatic insulinoma cells (β-TC6) and conducted a detailed analysis of the underlying molecular mechanisms. Herein, we demonstrate that Zyflamend treatment decreased cell proliferation in a dose-dependent manner, concomitant with increased apoptotic cell death and cell cycle arrest at the G2/M phase. At the molecular level, treatment with Zyflamend led to the induction of ER stress, autophagy, and the activation of c-Jun N-terminal kinase (JNK) pathway. Notably, pharmacological inhibition of JNK abrogated the pro-apoptotic effects of Zyflamend. Furthermore, Zyflamend exacerbated the effects of streptozotocin and adriamycin-induced ER stress, autophagy, and apoptosis. The current study identifies Zyflamend as a potential novel adjuvant in the treatment of pancreatic cancer via modulation of the JNK pathway.

中文翻译：

---

Zyflamend 通过调节 JNK 通路诱导胰腺癌细胞凋亡。

目前针对胰腺神经内分泌肿瘤 (PNET) 的药物疗法和治疗已被证明是无效的，而且经常发生。因此，迫切需要替代治疗方法。Zyflamend 是一种抗炎草药提取物的组合，已被证明在各种体外和体内癌症平台中均有效，显示出前景。然而，它对胰腺癌的影响，尤其是，在很大程度上仍未得到探索。在目前的研究中，我们研究了 Zyflamend 对 β-TC-6 胰腺胰岛素瘤细胞 (β-TC6) 存活的影响，并对潜在的分子机制进行了详细分析。在此，我们证明 Zyflamend 治疗以剂量依赖性方式降低细胞增殖，伴随着细胞凋亡增加和 G2/M 期细胞周期停滞。在分子水平上，用 Zyflamend 治疗导致 ER 应激、自噬和 c-Jun N 末端激酶 (JNK) 通路的激活。值得注意的是，JNK 的药理学抑制消除了 Zyflamend 的促凋亡作用。此外，Zyflamend 加剧了链脲佐菌素和阿霉素诱导的内质网应激、自噬和细胞凋亡的影响。目前的研究将 Zyflamend 确定为通过调节 JNK 途径治疗胰腺癌的潜在新型佐剂。自噬和细胞凋亡。目前的研究将 Zyflamend 确定为通过调节 JNK 途径治疗胰腺癌的潜在新型佐剂。自噬和细胞凋亡。目前的研究将 Zyflamend 确定为通过调节 JNK 途径治疗胰腺癌的潜在新型佐剂。