Watanabe Shunsuke, Suzuki Tatuya, Hara Fujio, Yasui Toshihiro, Uga Naoko, Naoe Atuki
Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
Pediatr Surg Int. 2017 Jun;33(6):713-719. doi: 10.1007/s00383-017-4069-4. Epub 2017 Mar 4.
Neuroblastoma is a refractory pediatric malignant solid tumor. The previous studies demonstrated that Polyphyllin D, the main constituent of Paris polyphylla, a traditional Chinese medicine, exerts an anti-tumor effect on many tumors. However, its effects against neuroblastomas are unclear.
We examined the anti-tumor effect of polyphyllin D in human neuroblastoma using IMR-32 and LA-N-2 cells, which exhibit MYCN gene amplification, and NB-69 cells, which do not exhibit MYCN gene amplification.
All cell lines showed reduced cell viability in response to polyphyllin D treatment. No caspase-3/-7, -8, and -9 activity was observed in IMR-32 and LA-N-2 cells treated with polyphyllin D. In contrast, activation of caspase-3/-7, and -8 activity was observed in NB-69 cells. When polyphyllin D and specific inhibitors of RIPK3 involved in necroptosis were added to IMR-32 and LA-N-2 cell lines, polyphyllin D-induced cell death was inhibited.
Together, this indicates that the underlying mechanism of polyphyllin D-induced cell death in NB-69 cells is apoptosis, whereas the cell death of IMR-32 and LA-N-2 cells occurs by necroptosis. We continue research on this topic and look forward the discovery of a new therapeutic agent for neuroblastoma.
神经母细胞瘤是一种难治性儿童恶性实体瘤。先前的研究表明，中药重楼的主要成分重楼皂苷D对多种肿瘤具有抗肿瘤作用。然而，其对神经母细胞瘤的作用尚不清楚。
我们使用表现出MYCN基因扩增的IMR-32和LA-N-2细胞以及未表现出MYCN基因扩增的NB-69细胞，研究了重楼皂苷D对人神经母细胞瘤的抗肿瘤作用。
所有细胞系在重楼皂苷D处理后细胞活力均降低。在用重楼皂苷D处理的IMR-32和LA-N-2细胞中未观察到半胱天冬酶-3/-7、-8和-9的活性。相反，在NB-69细胞中观察到半胱天冬酶-3/-7和-8活性的激活。当将重楼皂苷D和参与坏死性凋亡的RIPK3特异性抑制剂添加到IMR-32和LA-N-2细胞系中时，重楼皂苷D诱导的细胞死亡受到抑制。
综上所述，这表明重楼皂苷D诱导NB-69细胞死亡的潜在机制是凋亡，而IMR-32和LA-N-2细胞的死亡是通过坏死性凋亡发生的。我们将继续对这一课题进行研究，并期待发现一种治疗神经母细胞瘤的新治疗剂。
