Kreinest Teresa, Volkmer Ines, Staege Martin S
Department of Pediatrics I, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
Int J Mol Sci. 2020 Dec 31;22(1):343. doi: 10.3390/ijms22010343.
Hodgkin lymphoma (HL) is neoplasia with high cure rates. However, not all patients can be cured with the current treatment. Chemo-resistance of tumor cells is one factor involved in treatment failure. In addition to its pore-forming activity on lipid bilayer membranes, the toxin melittin from bee venom is an inhibitor of several cancer-related signaling pathways. Moreover, melittin analogs have been shown to inhibit the activity of ATP binding cassette (ABC) transporters which are known to play important roles in the chemo-resistance of tumor cells. Therefore, we tested the toxicity of melittin for HL cell lines KM-H2 and L-428 and whether melittin can increase the chemo-sensitivity of cisplatin-resistant HL cells. We found high toxicity of melittin for KM-H2 and L-428 cells. In co-cultures with normal blood cells, melittin preferentially killed KM-H2 and L-428 cells. In addition, we observed increased cisplatin sensitivity of chemo-resistant L-428 cells after treatment with melittin. ABC transporter activity was not reduced after treatment with melittin. Our data suggest that melittin or melittin analogs might be promising agents for the future development of treatment strategies for HL patients with resistant disease.
霍奇金淋巴瘤（HL）是一种治愈率很高的肿瘤。然而，并非所有患者都能通过当前治疗治愈。肿瘤细胞的化疗耐药性是导致治疗失败的一个因素。除了对脂质双分子层膜具有成孔活性外，蜂毒中的毒素蜂毒素还是几种癌症相关信号通路的抑制剂。此外，蜂毒素类似物已被证明可抑制ATP结合盒（ABC）转运蛋白的活性，而ABC转运蛋白在肿瘤细胞的化疗耐药性中起着重要作用。因此，我们测试了蜂毒素对HL细胞系KM-H2和L-428的毒性，以及蜂毒素是否能增加顺铂耐药HL细胞的化疗敏感性。我们发现蜂毒素对KM-H2和L-428细胞具有高毒性。在与正常血细胞共培养时，蜂毒素优先杀死KM-H2和L-428细胞。此外，我们观察到用蜂毒素处理后，化疗耐药的L-428细胞对顺铂的敏感性增加。用蜂毒素处理后，ABC转运蛋白活性并未降低。我们的数据表明，蜂毒素或蜂毒素类似物可能是未来开发针对耐药HL患者治疗策略的有前景的药物。
