目的 觀察鼻咽清毒顆粒逆轉(zhuǎn)鼻咽癌細(xì)胞順鉑耐藥的作用效應(yīng)，并探討其作用機(jī)制。方法 采用MTS法檢測系列質(zhì)量濃度鼻咽清毒顆粒對人鼻咽癌CNE-2、人鼻咽癌順鉑耐藥CNE2/DDP細(xì)胞增殖的抑制作用；計算鼻咽清毒顆粒對CNE-2、CNE2/DDP細(xì)胞的耐順鉑半數(shù)抑制濃度（IC₅₀）的影響；流式細(xì)胞技術(shù)測定CNE2/DDP的細(xì)胞凋亡情況；采用Western blotting法檢測CNE2/DDP細(xì)胞中銅轉(zhuǎn)運蛋白和抗凋亡蛋白的表達(dá)。結(jié)果 CNE2/DDP細(xì)胞的順鉑耐藥指數(shù)為RI值為3.03；與順鉑組比較，鼻咽清毒顆粒0.1、1、10 mg/mL組分別與系列質(zhì)量濃度的順鉑聯(lián)用，對CNE-2細(xì)胞順鉑IC₅₀分別降低12.19%、46.37%、63.81%；CNE2/DDP細(xì)胞順鉑IC₅₀分別降低61.75%、70.42%、83.82%。流式細(xì)胞技術(shù)檢測結(jié)果表明，與順鉑組比，順鉑＋鼻咽清毒顆粒0.1、1、10 mg/mL組CNE2-DDP晚期凋亡或壞死細(xì)胞增加（P＜0.01）；Western blotting法檢測結(jié)果表明，與順鉑組比較，順鉑＋鼻咽清毒顆粒0.1、1、10 mg/mL組銅特異性轉(zhuǎn)運蛋白（CTR1）蛋白的表達(dá)均顯著升高，B細(xì)胞淋巴瘤2（Bcl-2）、骨髓細(xì)胞白血病序列1（Mcl-1）的表達(dá)顯著降低（P＜0.05、0.01）。結(jié)論 鼻咽清毒顆粒具有增強(qiáng)鼻咽癌細(xì)胞順鉑敏感性、逆轉(zhuǎn)CNE2/DDP細(xì)胞順鉑耐藥作用，其作用機(jī)制可能與增加CTR1蛋白表達(dá)，降低Bcl-2、Mcl-1蛋白表達(dá)有關(guān)。

Objective To observe the effect of Biyan Qingdu Granules on reversing cisplatin resistance in nasopharyngeal carcinoma cells, and to explore its mechanism. Methods To detect the inhibitory effect of Biyan Qingdu Granules on the proliferation of CNE-2 and CNE2/DDP cells by MTS method. To calculate the effect of Biyan Qingdu Granules on cisplatin inhibiting IC₅₀ in CNE-2 and CNE2/DDP cells. The apoptosis of CNE2/DDP cells was determined by flow cytometry. The expressions of copper transporter and anti-apoptotic protein in CNE2/DDP cells were detected by Western Blotting. Results The cisplatin resistance index of CNE2/DDP cells was 3.03. Compared with cisplatin, the IC₅₀ of cisplatin in CNE-2 cells of 0.1, 1 and 10 mg/mL of Biyan Qingdu Granules was decreased by 12.19%, 46.37% and 63.81%, respectively. Cisplatin IC₅₀ in CNE2/DDP cells decreased by 61.75%, 70.42% and 83.82%, respectively. The results of flow cytometry showed that compared with cisplatin group, CNE2/DDP in Biyan Qingdu Granules 0.1, 1, 10 mg/mL groups increased late apoptosis or necrosis cells (P < 0.01). Western Blotting test results showed that compared with cisplatin group, the expression of copper specific transport protein (CTR1) in cisplatin + Biyan Qingdu Granules 0.1, 1 and 10 mg/mL groups was significantly increased. The expressions of B-cell lymphoma 2 (Bcl-2) and myeloid leukemia sequence 1 (Mcl-1) were significantly decreased (P < 0.05, 0.01). Conclusion Biyan Qingdu Granules can enhance the cisplatin sensitivity of nasopharyngeal carcinoma cells and reverse the cisplatin resistance of CNE2/DDP cells, and its mechanism may be related to increasing the expression of CTR1 protein and decreasing the expression of Bcl-2 and Mcl-1 protein.

R979.1

廣州市科技計劃項目（20212210006）