Page 53 - 《中国药房》2023年1期
P. 53

徐长卿中的天然产物 XCQ-9 对 Jurkat 细胞增殖和凋亡的影响及

          机制研究
                        Δ


                                     1, 2
                                              1, 2
                                                        3
                           1, 2
                                                                1, 2 #
          韦学耐    1, 2* ,杨 坤 ,刘 琴 ,赵 鹏 ,晏 英 ,李艳梅 (1.贵州医科大学药学院,贵阳 550025;2.贵州
          省中国科学院天然产物化学重点实验室,贵阳 550014;3.贵州医科大学医药卫生管理学院,贵阳 550025)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)01-0047-05
          DOI  10.6039/j.issn.1001-0408.2023.01.09

          摘  要  目的  探讨徐长卿中天然产物XCQ-9抑制人急性T淋巴细胞白血病Jurkat细胞增殖和凋亡的作用及可能机制。方法  以
          Jurkat细胞作为白血病细胞模型,采用MTT法测定0(空白对照)、2.5、5、10、20、40 μmol/L XCQ-9作用24、48、72 h后对Jurkat细胞
          增殖的抑制作用。用0(空白对照)、2.5、5、10 μmol/L XCQ-9作用于Jurkat细胞24、48 h后,利用流式细胞术分析XCQ-9对细胞周
          期和细胞凋亡的影响,并通过 Western blot 实验检测上述药物作用 24 h 后细胞中胱天蛋白酶 9(Caspase-9)、活化的 Caspase-9
         (Cleaved Caspase-9)、Caspase-3、活化的Caspase-3(Cleaved Caspase-3)、聚腺苷二磷酸-核糖聚合酶(PARP)、活化的PARP(Cleaved
          PARP)、细胞周期蛋白依赖性激酶1(CDK1)和细胞周期蛋白B1(Cyclin B1)的表达情况。结果  与空白对照比较,不同浓度XCQ-9
          均可显著降低Jurkat细胞的存活率(P<0.01),并呈时间和浓度依赖性趋势。5、10 μmol/L XCQ-9作用48 h后均可显著诱导Jurkat细胞
          凋亡(P<0.05或P<0.01),将细胞周期阻滞在G2期(P<0.01)。10 μmol/L XCQ-9作用24 h后,可显著下调细胞中CDK1、Caspase-9
          蛋白的表达(P<0.01),上调细胞中 Cyclin B1、Cleaved Caspase-9、Cleaved Caspase-3 和 Cleaved PARP 蛋白的表达(P<0.05 或 P<
          0.01)。结论  XCQ-9通过诱导G2期阻滞抑制Jurkat细胞增殖,并激活Caspase通路促进细胞凋亡,从而发挥其抗肿瘤作用。
          关键词  XCQ-9;徐长卿;人急性T淋巴细胞白血病;Jurkat细胞;细胞凋亡;细胞周期;胱天蛋白酶途径

          Study  on  the  effect  of  natural  compound  XCQ-9  of  Cynanchum  paniculatum  on  the  proliferation  and
          apoptosis of Jurkat cell and its mechanism
                                            1, 2
          WEI Xuenai ,YANG Kun ,LIU Qin ,ZHAO Peng ,YAN Ying ,LI Yanmei (1. School of Pharmaceutical,
                                                                                1, 2
                                 1, 2
                    1, 2
                                                         1, 2
                                                                     3
          Guizhou  Medical  University,  Guiyang  550025,  China;2.  Key  Laboratory  of  Chemistry  for  Natural  Products,
          Guizhou  Province  and  Chinese  Academy  of  Sciences,  Guiyang  550014,  China;3.  School  of  Medicine  and
          Health Management, Guizhou Medical University, Guiyang 550025, China)
          ABSTRACT   OBJECTIVE  To  investigate  the  inhibitory  effect  of  natural  compound  XCQ-9  of  Cynanchum  paniculatum  on  the
          proliferation  and  apoptosis  of  Jurkat  cell  line  of  human  T-cell  acute  lymphoblastic  leukemia  and  its  possible  mechanism.
          METHODS  Jurkat  cell  was  used  as  the  leukemia  cell  model,  and  MTT  assay  was  adopted  to  detect  the  inhibitory  effects  of  0
         (blank  control),  2.5,  5,  10,  20  and  40  μmol/L  XCQ-9  on  the  proliferation  of  Jurkat  cell  after  treated  for  24,  48,  72  h. After
          treated with 0 (blank control), 2.5, 5, 10 μmol/L XCQ-9 for 24 h and 48 h, the cell cycle and apoptosis were analyzed by flow
          cytometry.  The  expressions  of  Caspase-9,  Cleaved  Caspase-9,  Caspase-3,  Cleaved  Caspase-3,  poly  ADP-ribose  poly-merase
         (PARP),  Cleaved-PARP,  cyclin-dependent  kinase  1 (CDK1)  and  Cyclin  B1  were  detected  by Western  blot  after  treated  for  24  h.
          RESULTS  Compared  with  blank  control  group,  XCQ-9  at  different  concentrations  could  significantly  decrease  the  survival  rate  of
          Jurkat cells (P<0.01), and showed a dose and time-dependent manner. After 48 h treatment of 5, 10 μmol/L XCQ-9, Jurkat cell
          apoptosis was induced significantly (P<0.05 or P<0.01), and the cell was arrested in G2 phase (P<0.01). After 24 h treatment of
          10 μmol/L XCQ-9, the protein expressions of CDK1 and Caspase-9 were remarkably down-regulated (P<0.01), while the protein
          expressions  of  Cyclin  B1,  Cleaved  Caspase-9,  Cleaved  Caspase-3  and  Cleaved  PARP  were  significantly  up-regulated (P<0.05  or
                                                             P<0.01).  CONCLUSIONS  XCQ-9  plays  anti-tumor  effect
             Δ 基金项目 国 家 自 然 科 学 基 金 资 助 项 目(No. 81872772,No.
                                                             through  inducing  G2  phase  arrest  to  inhibit  proliferation  and
          81960546,No.U1812403);贵州省科技计划项目(No.QKHPTRC〔2020〕
          5008)                                              activating Caspase pathway to increase apoptosis.
             *第一作者 硕士研究生。研究方向:小分子化合物抗肿瘤基础。                   KEYWORDS     XCQ-9;  Cynanchum  paniculatum;  human  T-
          E-mail:2531392591@qq.com                           cell  acute  lymphoblastic  leukemia;  Jurkat  cell;  cell  apoptosis;
             # 通信作者 研究员,硕士生导师,博士。研究方向:小分子化合物                 cell cycle; Caspase pathway
          抗肿瘤基础。电话:0851-83834026。E-mail:liyanmei518@hotmail.
          com


          中国药房  2023年第34卷第1期                                                  China Pharmacy  2023 Vol. 34  No. 1    · 47 ·
   48   49   50   51   52   53   54   55   56   57   58