胆管癌（CCA）是一种预后不良的恶性肿瘤，对传统化疗药物无效。急需有效和新颖的治疗药物。VR12684（来自槐果黄籽）据报道在癌细胞系中表现出抑制生长的活性。本研究对该化合物在人类CCA细胞株KKU-M-156中的抑制生长机制进行了研究。通过SRB法、流式细胞术、乙烯溴化乙啶/AO染色和蛋白质印迹分析，证明VR12684对CCA细胞的抗增殖、细胞周期阻滞和诱导凋亡等作用。在KKU-M-156细胞株中，VR12684的处理以剂量和时间依赖的方式降低了细胞增殖。VR12684通过调节周期素B1、细胞周期蛋白依赖激酶1的表达水平下调，p21、p27和p53的表达水平上调诱导KKU-M-156细胞在G2期细胞周期阻滞。VR12684通过增加DNA断裂、Bax/Bcl-2比值和AIF、减少survivin以及触发caspase-9和caspase-3的活化，诱导线粒体介导的凋亡。该化合物还可通过内质网应激介导的路径诱导凋亡，上调GRP78、IRE1α和GADD153的表达水平，下调Bcl-2的表达水平，激活calpain-1、caspase-7和caspase-12。这些结果表明，VR12684通过细胞周期阻滞和诱导凋亡的方式抑制了KKU-M-156细胞的生长，至少部分通过线粒体和内质网相关的内源途径实现。这些化合物值得作为人类CCA治疗的候选药物进行评估。

Cholangiocarcinoma (CCA) is a poor prognosis of a malignant tumor that has been unresponsive to conventional chemotherapeutic agents. Effective and novel therapeutic agents are urgently needed. VR12684 (isolated from Mallotus spodocarpus) has been reported to exhibit growth inhibitory activities in cancer cell lines. The present study investigated the growth inhibitory mechanisms of this compound in a human CCA cell line (KKU-M156).The effects of VR12684 on anti‑proliferation, cell cycle arrest and apoptosis induction in CCA cells were demonstrated by SRB assay, flow cytometry, acridine orange/ethidium bromide (AO/EB) staining and western blot analysis.Treatment with VR12684 decreased cell proliferation in a dose- and time-dependent manner in the KKU-M156 cell line. VR12684 induced cell cycle arrest in the G2 phase in KKU-M156 through down-regulation of cyclin B1 and Cdk1 and up-regulation of p21, p27 and p53 levels. VR12684 induced mitochondria-mediated apoptosis by increasing DNA fragmentation, the Bax/BCL-2 ratio and AIF, and decreasing survivin with subsequent activation of caspase-9 and -3. This compound could induce apoptosis through the endoplasmic reticulum (ER) stress-mediated pathway by up-regulation of GRP78, IRE1α and GADD153 levels leading to down-regulation of Bcl-2 and activation of calpain-1, caspase-7 and -12.These results suggested that VR12684 inhibited KKU-M-156 cell growth by way of cell cycle arrest and induction of apoptosis, at least in part, through the mitochondria- and ER-associated intrinsic pathways. Such compounds warrant evaluation as a candidate for the treatment of human CCA.