热发性细胞死亡是一种新近鉴定的细胞死亡形式，其形态学特征为细胞肿胀过度。本研究中，使用紫杉醇（PTX）与铂类合药作为卵巢癌细胞的一线化疗，诱导多种细胞死亡。但PTX是否能够诱导卵巢癌细胞发生热发性细胞死亡仍不清楚。最近的报道显示，PTX能抑制氯通道，这种抑制作用是导致细胞肿胀的原因之一。本研究首次证实，PTX能够在A2780卵巢癌细胞中诱导类似热发性细胞死亡、被切割的Caspase-3和被切割的气孔形态E (GSDME)。PTX能够抑制背景电流和低渗透压激活的氯电流，促进细胞内氯离子蓄积，这些表现类似于VRAC经典体积调节型阴离子通道（VRAC）阻滞剂，4-（2-丁基-6，7-二氯-2-环戊基-1-酮-5-基）氧基丁酸（DCPIB）。需要注意的是，DCPIB和VRAC的组分蛋白leucine-rich repeat-containing 8a的下调本身无法诱导细胞肿胀和类似热发性细胞死亡的表型。然而，它们可以增强PTX诱导类似热发性细胞死亡的效果，如明显的细胞肿胀、细胞膜破裂和过度激活Caspase-3和GSDME N端片段，最终在A2780细胞中导致明显的热发性细胞死亡。这些发现揭示了PTX的潜在机制，并提供了PTX与VRAC阻滞剂协同用于卵巢癌化疗的新思路。

Pyroptosis is a newly identified form of cell death, morphologically characterized by excessive cell swelling. In the present study, paclitaxel (PTX) combined with platinum were used as first‑line chemotherapy, against ovarian cancer cells by inducing multiple types of cell death. However, it remains unclear whether PTX can induce pyroptosis in ovarian cancer cells. It was recently reported that PTX inhibited chloride channels, an inhibition known to cause cell swelling. In the present study, it was first verified that pyroptosis‑like cell death, as well as cleaved‑caspase‑3 and cleaved‑gasdermin E (GSDME) were induced by PTX in A2780 ovarian cancer cells. PTX inhibited the background‑ and hypotonicity‑activated chloride currents, promoted intracellular chloride ion accumulation, those manifestations are similar to those of the classic volume‑regulatory anion channel (VRAC) blocker, 4‑(2‑butyl‑6,7‑dichloro‑2‑cy-clopentyl‑indan‑1‑on5‑yl) oxobutyric acid (DCPIB). Of note, both DCPIB and the downregulation of VRAC constituent protein leucine‑rich repeat‑containing 8a themselves could not induce persisted cell swelling and pyroptosis‑like phenotypes. However, they could enhance the effects of PTX in inducing pyroptosis‑like phenotypes, such as marked cell swelling, cell membrane rupture and excessive activation of caspase‑3 and GSDME N‑terminal fragment, which ultimately caused marked pyroptosis in A2780 cells. These findings revealed a potential mechanism of PTX and offered new insights into the effects of a synergistical combination of PTX and VRACs blockers in ovarian cancer chemotherapy.