Ni Zhen, Dawa Zhuoma, Suolang Deji, Pingcuo Quzhen, Langga Zhuoma, Quzhen Pingcuo, Deji Zhuoga
Department of Pathology, General Hospital of The Tibetan Military Region of The Chinese People's Liberation Army, Lhasa, Tibet Autonomous Region 850000, P.R. China.
Basic Department, Medical College of Tibet University, Lhasa, Tibet Autonomous Region 850000, P.R. China.
Oncol Lett. 2023 Feb 15;25(4):136. doi: 10.3892/ol.2023.13722. eCollection 2023 Apr.
Endometrial cancer (EC) is a complex disease that affects the reproductive health of females worldwide. Platycodin D (PD) is known to exert numerous anticancer effects, markedly inhibiting cell proliferation, inducing apoptosis and causing cell cycle arrest in several types of cancer. The present study aimed to explore the mechanisms underlying the effects of PD in EC cells. The viability and proliferation of human endometrial stromal cells (ESCs) and RL95-2 EC cells following treatment with PD were evaluated using Cell Counting Kit-8, MTT and colony formation assays. Wound healing and Transwell assays were also performed to assess the migration and invasion of EC cells following treatment with PD. The expression levels of α2A-adrenergic receptor (ADRA2A) were measured using reverse transcription-quantitative PCR and western blotting assays with and without PD treatment and following transfection with short hairpin (sh) RNAs targeting ADRA2A2. Moreover, western blot analysis was performed to measure the expression levels of Ki67, PCNA, MMP2 and MMP9 and the phosphorylation of proteins of the PI3K/Akt signaling pathway. The results demonstrated that treatment with PD markedly decreased the proliferation, invasion and migration of EC cells, and reduced activation of the PI3K/Akt signaling pathway in EC cells. Moreover, transfection with sh-ADRA2A attenuated the effects of PD. ADRA2A expression was downregulated in EC cells compared with ESCs, and ADRA2A expression was elevated in EC cells following treatment with PD. In conclusion, the present study indicates that PD blocked the PI3K/Akt signaling pathway via the upregulation of ADRA2A expression, thereby inhibiting the proliferation, invasion and migration of EC cells.
子宫内膜癌（EC）是一种复杂的疾病，影响着全球女性的生殖健康。已知桔梗皂苷D（PD）具有多种抗癌作用，能显著抑制多种癌症类型的细胞增殖、诱导细胞凋亡并导致细胞周期停滞。本研究旨在探讨PD对EC细胞作用的潜在机制。使用细胞计数试剂盒-8、MTT和集落形成试验评估PD处理后人子宫内膜基质细胞（ESCs）和RL95-2 EC细胞的活力和增殖。还进行了伤口愈合试验和Transwell试验，以评估PD处理后EC细胞的迁移和侵袭能力。使用逆转录定量PCR和蛋白质印迹试验，在有无PD处理以及用靶向ADRA2A的短发夹（sh）RNA转染后，测量α2A-肾上腺素能受体（ADRA2A）的表达水平。此外，进行蛋白质印迹分析以测量Ki67、PCNA、MMP2和MMP9的表达水平以及PI3K/Akt信号通路蛋白的磷酸化水平。结果表明，PD处理显著降低了EC细胞的增殖、侵袭和迁移能力，并降低了EC细胞中PI3K/Akt信号通路的激活。此外，用sh-ADRA2A转染减弱了PD的作用。与ESCs相比，EC细胞中ADRA2A表达下调，PD处理后EC细胞中ADRA2A表达升高。总之，本研究表明，PD通过上调ADRA2A表达阻断PI3K/Akt信号通路，从而抑制EC细胞的增殖、侵袭和迁移。
