The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer.
The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer.
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三萜乙醇素B增强了人类乳腺癌化学疗法的抗增殖活性。
DOI：
10.1002/ijc.27950
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发表时间：
2013-06-15
影响因子：
6.4
通讯作者：
Koeffler, H. Phillip
中科院分区：
文献类型：
--
作者：
Aribi, Ahmed;Gery, Sigal;Lee, Dhong Hyun;Thoennissen, Nils H.;Thoennissen, Gabriela B.;Alvarez, Rocio;Quoc Ho;Lee, Kunik;Doan, Ngan B.;Chan, Kin T.;Toh, Melvin;Said, Jonathan W.;Koeffler, H. Phillip
尽管最近在治疗方面取得了进展，但乳腺癌仍然是女性恶性肿瘤死亡的第二大常见原因。化疗在乳腺癌治疗中起着重要作用，联合化疗药物与非化疗药物具有相当大的临床意义。葫芦素是在葫芦科植物中发现的三萜类化合物，据报道具有抗癌和抗炎活性。以前，我们已经显示葫芦素B（Cu B）在乳腺癌中的抗增殖活性，我们假设将Cu B与化疗药物结合可以增强其抗肿瘤作用。在这里，我们表明，CuB与多西他赛（DOC）或吉西他滨（GEM）的组合在体外协同抑制MDA-MB-231乳腺癌细胞的增殖。这种抗增殖作用伴随着细胞凋亡率的增加。此外，与每种药物的单药治疗相比，用低剂量（0.5 mg/kg）或高剂量（1 mg/kg）的CuB与DOC（20 mg/kg）或GEM（12.5 mg/kg）组合在免疫缺陷小鼠中体内治疗人乳腺癌原位异种移植物显著减小了肿瘤体积。重要的是，低剂量CuB与DOC或GEM组合没有观察到显著的毒性。总之，在一个相对较低的浓度与化疗剂，DOC或GEM的CuB的组合，显示出突出的抗增殖活性对乳腺癌细胞没有增加的毒性。这种有希望的组合应该在乳腺癌的治疗试验中进行检查。
Despite recent advances in therapy, breast cancer remains the second most common cause of death from malignancy in women. Chemotherapy plays a major role in breast cancer management, and combining chemotherapeutic agents with non-chemotherapeutic agents is of considerable clinical interest. Cucurbitacins are triterpenes compounds found in plants of the Cucurbitaceae family, reported to have anti-cancer and anti-inflamatory activities. Previously, we have shown antiproliferative activity of cucurbitacin B (CuB) in breast cancer, and we hypothesized that combining CuB with chemotherapeutic agents can augment their anti-tumor effect. Here, we show that a combination of CuB with either docetaxel (DOC) or gemcitabine (GEM) synergistically inhibited the proliferation of MDA-MB-231 breast cancer cells in vitro. This antiproliferative effect was accompanied by an increase in apoptosis rates. Furthermore, in vivo treatment of human breast cancer orthotopic xenografts in immunodeficient mice with CuB at either low (0.5 mg/kg) or high (1 mg/kg) doses in combination with either DOC (20 mg/kg) or GEM (12.5 mg/kg) significantly reduced tumor volume as compared to monotherapy of each drug. Importantly, no significant toxicity was noted with low dose CuB in combination with either DOC or GEM. In conclusion, combination of CuB at a relatively low concentration with either of the chemotherapeutic agents, DOC or GEM, shows prominent antiproliferative activity against breast cancer cells without increased toxicity. This promising combination should be examined in therapeutic trials of breast cancer.
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影响因子：
45.3
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