Department of Abdominal Radiotherapy, Hubei Provincial Cancer Hospital, Wuhan, China.
Colorectal Cancer Clinical Medical Research Center of Hubei Province, Wuhan, China.
J Pharm Pharmacol. 2023 Apr 17;75(5):645-654. doi: 10.1093/jpp/rgad008.
The primary goal of the current study was to investigate the effect of melittin on colorectal cancer (CRC).
The viability of cancer cells was tested using the MTT assay, and the apoptosis of tumour cells was assayed using Annexin V/PI staining in vitro or TUNEL staining in vivo. The in vivo toxicity and efficacy of melittin were assessed in a xenograft mouse model.
Melittin inhibited the viability of CRC cell lines and induced apoptosis in SW480 cells by regulating apoptosis-related proteins. Melittin triggered endoplasmic reticulum (ER) stress and caused an imbalance in calcium homeostasis in SW480 cells. An absence of melittin triggered ER stress via the calcium chelating agent BAPTA/AM, and the IP3R inhibitor 2-aminoethoxydiphenyl borate (2-APB) impaired melittin-induced apoptosis in SW480 cells. Melittin treatment suppressed tumour growth but did not affect the body weight of SW480 tumour-bearing mice. Unlike cisplatin and 5-fluorouracil, melittin treatment did not change the biochemical and haematological parameters of the tumour-bearing mice. Finally, in these mice, melittin treatment induced ER stress, which was then blocked by BAPTA/AM, whilst 2-APB impaired the growth inhibitory effect of melittin.
Melittin treatment inhibits CRC progression by inducing ER stress and an imbalance in calcium homeostasis.
本研究的主要目的是研究蜂毒素对结直肠癌（CRC）的影响。
通过 MTT 法检测癌细胞活力，通过 Annexin V/PI 染色法或 TUNEL 染色法在体外或体内检测肿瘤细胞凋亡。通过异种移植小鼠模型评估蜂毒素的体内毒性和疗效。
蜂毒素通过调节凋亡相关蛋白抑制 CRC 细胞系的活力并诱导 SW480 细胞凋亡。蜂毒素引发内质网（ER）应激，并导致 SW480 细胞中钙稳态失衡。通过钙螯合剂 BAPTA/AM 去除蜂毒素会触发 ER 应激，而 IP3R 抑制剂 2-APB 会损害 SW480 细胞中蜂毒素诱导的凋亡。蜂毒素治疗抑制肿瘤生长，但不影响 SW480 荷瘤小鼠的体重。与顺铂和 5-氟尿嘧啶不同，蜂毒素治疗不会改变荷瘤小鼠的生化和血液学参数。最后，在这些小鼠中，蜂毒素治疗诱导 ER 应激，然后被 BAPTA/AM 阻断，而 2-APB 则损害了蜂毒素的生长抑制作用。
蜂毒素通过诱导 ER 应激和钙稳态失衡抑制 CRC 进展。
