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CD133 表达对腺样囊性癌化疗及药物敏感性的影响。

Effects of CD133 expression on chemotherapy and drug sensitivity of adenoid cystic carcinoma.

机构信息

Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, P.R. China.

出版信息

Mol Med Rep. 2022 Jan;25(1). doi: 10.3892/mmr.2021.12534. Epub 2021 Nov 18.

Abstract

The cellular resistance of tumors is a major obstacle for successful tumor therapy. Cluster of differentiation (CD)133 plays an important role in the regulation of drug resistance in gastric and colon cancers. However, its effect on chemotherapeutic sensitivity in adenoid cystic carcinoma (ACC) has not been fully explored. The present study discussed the specific role of CD133 in ACC drug‑resistant sensitive cells. KOA‑1 cells were treated with 5‑fluorouracil (5‑FU) and pingyangmycin (PYM) to form drug‑resistant cell lines. A Cell Counting Kit‑8 assay was used to detect the cell survival rate. Cell invasion was measured using a Transwell assay. The expression levels of CD133 were detected by reverse transcription‑quantitative (RT‑q) PCR. The expression levels of drug‑resistant mRNAs and proteins were detected by RT‑qPCR and immunofluorescence analyses, respectively. The CD133 were inhibited by small interfering RNA technology. The survival rate and invasive ability of KOA‑1 cells were increased following the induction of drug resistance. The expression levels of CD133, multidrug resistance protein (MDR)1 and multidrug resistance‑associated protein (MRP)1 were significantly increased in drug‑resistant cell lines. Knockdown of CD133 expression in the resistant cell lines, KOA‑1/5‑FU and KOA‑1/PYM, decreased the survival rate and invasive ability. The expression levels of MDR1 and MRP1 were also significantly decreased. Knockdown of CD133 expression in ACC drug‑resistant cells could inhibit the viability and invasion of tumors and enhance the sensitivity of drug‑resistant cells to chemotherapeutic drugs.

摘要

肿瘤细胞的耐药性是肿瘤治疗成功的主要障碍。分化簇(CD)133 在调节胃癌和结肠癌的耐药性方面发挥着重要作用。然而,其在腺样囊性癌(ACC)中对化疗敏感性的影响尚未得到充分探索。本研究探讨了 CD133 在 ACC 耐药敏感细胞中的具体作用。用 5-氟尿嘧啶(5-FU)和平阳霉素(PYM)处理 KOA-1 细胞,以形成耐药细胞系。使用细胞计数试剂盒-8 检测细胞存活率。使用 Transwell 测定法测量细胞侵袭。通过逆转录-定量(RT-q)PCR 检测 CD133 的表达水平。通过 RT-qPCR 和免疫荧光分析分别检测耐药 mRNA 和蛋白的表达水平。通过小干扰 RNA 技术抑制 CD133 的表达。耐药诱导后,KOA-1 细胞的存活率和侵袭能力增加。耐药细胞系中 CD133、多药耐药蛋白(MDR)1 和多药耐药相关蛋白(MRP)1 的表达水平显著增加。在耐药细胞系 KOA-1/5-FU 和 KOA-1/PYM 中敲低 CD133 表达降低了存活率和侵袭能力。MDR1 和 MRP1 的表达水平也显著降低。敲低 ACC 耐药细胞中的 CD133 表达可抑制肿瘤的活力和侵袭,并增强耐药细胞对化疗药物的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9f8/8619834/15b44f85ebfe/mmr-25-01-12534-g00.jpg

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