The effect of paclitaxel and nab-paclitaxel in combination with anti-angiogenic therapy in breast cancer cell lines
The effect of paclitaxel and nab-paclitaxel in combination with anti-angiogenic therapy in breast cancer cell lines
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紫杉醇和白蛋白结合型紫杉醇联合抗血管生成治疗对乳腺癌细胞系的影响
作者：
F. Tonissi;L. Lattanzio;M. Merlano;L. Infante;C. Lo Nigro;O. Garrone
摘要紫杉烷类药物代表了转移性乳腺癌的一种治疗选择。它们与贝伐珠单抗的组合提高了缓解率和无进展生存期。我们在体外研究了紫杉醇或白蛋白结合型紫杉醇与贝伐单抗的组合对细胞存活的影响，并研究了与治疗反应有关的生物学因素。我们使用了两种乳腺癌细胞系 MCF7 (ER+/HER2-) 和 MDA-MB-231 (ER-/HER2-)，与或不与 HUVEC 细胞共培养。我们通过 MTT 测试分析细胞存活，通过 ELISA 分析 VEGF 分泌，通过蛋白质印迹分析 VEGFR、SPARC、MDR1 表达。在 MCF7 中引起 50% 生长抑制的两种紫杉烷剂量高于 MDA-MB-231，表明紫杉烷在 ER 细胞系中更有效。当两种细胞系作为单一培养物生长时，贝伐单抗+紫杉醇的组合与单独的紫杉醇相比显示出相似的抗增殖作用。贝伐单抗+白蛋白结合型紫杉醇的联合比单独的白蛋白结合型紫杉醇更有效。当 MDA-MB-231 细胞与 HUVEC 一起培养时，观察到贝伐单抗 + 紫杉醇的抗增殖作用增强。当 MDA-MB-231 细胞用任一紫杉烷处理时，我们检测到 VEGF 分泌的诱导。紫杉醇导致 MCF7 中 VEGF 的减少。在用贝伐单抗+白蛋白结合型紫杉醇处理的两种细胞系中，SPARC 结果上调。与单独使用紫杉烷类药物相比，白蛋白结合型紫杉醇似乎在两种乳腺癌细胞中通过与贝伐珠单抗结合的白蛋白-SPARC 抑制肿瘤增殖发挥重要作用。在紫杉醇中添加贝伐单抗仅增加了 ER-细胞的活性。这种差异可能是由于他们的急诊状态所致。
SummaryTaxanes represent a treatment of choice for metastatic breast cancer. Their combination with bevacizumab improved response rate and progression-free survival. We studied in vitro the effect on cell survival of the combination of either paclitaxel or nab-paclitaxel with bevacizumab and we investigated the biological factors involved in the response to treatments. We used two breast cancer cell lines, MCF7 (ER+/HER2-) and MDA-MB-231 (ER-/HER2-), co-cultured with or without HUVEC cells. We analysed cell survival by MTT test, VEGF secretion by ELISA and VEGFR, SPARC, MDR1 expression by western blot. Doses of both taxanes causing a 50 % growth inhibition were higher in MCF7 than MDA-MB-231, suggesting that taxanes are more effective in ER- cell lines. When both cell lines were grown as single culture, the combination bevacizumab+paclitaxel showed a similar anti-proliferative effect compared to paclitaxel alone. The association bevacizumab+nab-paclitaxel was more effective than nab-paclitaxel alone. An increased anti-proliferative effect of bevacizumab+paclitaxel was observed when MDA-MB-231 cells were cultured with HUVEC. We detected an induction of VEGF secretion when MDA-MB-231 cells were treated with either taxanes. Paclitaxel caused a reduction of VEGF in MCF7. SPARC resulted up-regulated in both cell lines treated with bevacizumab+nab-paclitaxel. Nab-paclitaxel seems to play an important role in inhibiting tumor proliferation through albumin-SPARC bound in association with bevacizumab compared to taxanes alone in both breast cancer cells. The addition of bevacizumab to paclitaxel increased its activity only in ER- cells. This difference might be due to their ER status.
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DOI：
10.1073/pnas.96.23.13369
发表时间：
1999-11-09
影响因子：
11.1
作者：
Li, CJ;Li, YZ;Pardee, AB
通讯作者：
Pardee, AB
影响因子：
--
作者：
SCHNITZER, JE;OH, P
通讯作者：
OH, P
影响因子：
11.2
作者：
McDaid, HM;Lopez-Barcons, L;Horwitz, SB
通讯作者：
Horwitz, SB
影响因子：
4.8
作者：
Volk, Lisa D.;Flister, Michael J.;Ran, Sophia
通讯作者：
Ran, Sophia
影响因子：
45.3
作者：
Winer, EP;Berry, DA;Norton, L
通讯作者：
Norton, L