Tumor-associated fibroblast-conditioned medium induces CDDP resistance in HNSCC cells.
Tumor-associated fibroblast-conditioned medium induces CDDP resistance in HNSCC cells.
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DOI：
10.18632/oncotarget.6210
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发表时间：
2016-01-19
期刊：
影响因子：
--
通讯作者：
Dudas J
中科院分区：
文献类型：
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作者：
Steinbichler TB;Metzler V;Pritz C;Riechelmann H;Dudas J
EMT(上皮向间充质转化)有助于肿瘤的进展和转移。本研究旨在探讨EMT对头颈部鳞状细胞癌(HNSCC)细胞顺铂耐药的影响。用肿瘤细胞/成纤维细胞共培养的条件培养液诱导EMT。将转化生长因子-β-1交替作用于HNSCC细胞，通过细胞存活率和克隆形成实验评价细胞对CDDP的反应。用条件培养液处理SCC-25/Detroit 562细胞可提高肿瘤细胞的存活率。此外，它还使SCC-25细胞顺铂的IC_(50)从6.2μM增加到13.1μM(p<；0.001)。经条件培养液处理后，底特律562细胞对顺铂的IC_(50)由13.1μM增加到26.8μM(p<；0.01)。经5或10μM顺铂处理后，共培养条件培养液处理的HNSCC细胞的集落形成能力明显高于对照组(p<；0.05)。转化生长因子-β-1对顺铂的IC50值无影响(p>；0.1)。共培养的无细胞培养液可诱导HNSCC细胞发生EMT。共培养的HNSCC细胞存活率增加，对CDDP的敏感性降低。转化生长因子-β-1也可诱导细胞间充质表型，但不改变细胞对顺铂的耐药性。
EMT (epithelial to mesenchymal transition) contributes to tumor progression and metastasis. We aimed to investigate the effects of EMT on CDDP resistance in HNSCC (head and neck squamous cell carcinoma)-cells. EMT was induced using conditioned medium from a tumor cell/fibroblast co-culture. HNSCC cells were alternatively treated with TGF-β1. The response to CDDP was evaluated with viability and clonogenic assays. Treatment of SCC-25/Detroit 562 cells with conditioned medium increased viability of the tumor cells. Moreover, it doubled the IC50 of CDDP of SCC-25 cells from 6.2 μM to 13.1 μM (p < 0.001). The IC50 of CDDP of Detroit 562 cells was increased following treatment with conditioned medium from 13.1 μM to 26.8 μM (p < 0.01). Colony forming ability after treatment with 5 or 10 μM CDDP was significantly higher in HNSCC cells treated with co-culture conditioned medium than in controls (p < 0.05). Treatment with TGF-β1 had no effect on the IC50 of CDDP (p > 0.1). Cell free medium from a co-culture was able to induce EMT in HNSCC cells. Co-culture treated HNSCC cells revealed increased viability and were less sensitive to CDDP treatment. TGF-β1 also induced a mesenchymal phenotype, but did not alter resistance to CDDP in HNSCC cells.