Jin Hao, Jin Xin, Cao Boran, Wang Wenbo
Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Oncol Rep. 2017 Feb;37(2):729-736. doi: 10.3892/or.2016.5327. Epub 2016 Dec 16.
Osteosarcoma is one of the most devastating cancers with associated poor prognosis. Chronic bone inflammation frequently predisposes to tumorigenesis and progression of osteosarcoma. In the tumor inflammatory microenvironment, caspase-1 and its processed cytokines such as interleukin 1β (IL-1β) play an important role in the occurrence and development of cancer. Berberine is an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, which has been found to exhibit significant anticancer effects on a wide spectrum of carcinomas including osteosarcoma. However, the mechanisms underlying the anticancer effects of berberine in osteosarcoma remain poorly understood and their elucidation is critical for developing improved therapies. In the present study, we investigated the potential mechanism underlying the anticancer effect of berberine in osteosarcoma. We found that the expression of caspase-1 and its downstream target IL-1β were higher in osteosarcoma cells compared with normal cells both in vitro and in vivo. Furthermore, administration of berberine is capable of reducing the expression of caspase-1 and IL-1β in osteosarcoma cells and inhibiting the growth of tumor cells. Based on the above, for the first time, we propose the hyposis that berberine could gengerate an anti-osteosarcoma property through downregulating caspase-1/IL-1β inflammatory signaling axis.
骨肉瘤是最具毁灭性的癌症之一，预后较差。慢性骨炎症常易引发骨肉瘤的肿瘤发生和进展。在肿瘤炎性微环境中，半胱天冬酶-1及其加工后的细胞因子如白细胞介素1β（IL-1β）在癌症的发生和发展中起重要作用。黄连素是从黄连干燥根中提取的一种异喹啉生物碱，已发现其对包括骨肉瘤在内的多种癌症具有显著的抗癌作用。然而，黄连素在骨肉瘤中的抗癌作用机制仍知之甚少，阐明这些机制对于开发改进的治疗方法至关重要。在本研究中，我们调查了黄连素在骨肉瘤中抗癌作用的潜在机制。我们发现，在体外和体内，骨肉瘤细胞中半胱天冬酶-1及其下游靶点IL-1β的表达均高于正常细胞。此外，给予黄连素能够降低骨肉瘤细胞中半胱天冬酶-1和IL-1β的表达，并抑制肿瘤细胞的生长。基于以上研究，我们首次提出假说，即黄连素可能通过下调半胱天冬酶-1/IL-1β炎性信号轴产生抗骨肉瘤特性。
