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第44卷第10期         王薇雅,陶长锐,晁红颖,等. 三氧化二砷联合普纳替尼对白血病细胞KG⁃1的抑制效应[J].
                 2024年10月                    南京医科大学学报(自然科学版),2024,44(10):1362-1368                      ·1365 ·


                  A   100                         B                                C               ***
                     (%)  80                          (%)  60                         (%)  30  **  **  ***  **

                     Inhibition ratio  60             Inhibition ratio  40             20
                       40
                                                       20
                       20
                        0                                                             Inhibition ratio  10
                           0  5 10 20 40 60 80 100     0                                0
                               ATO(μg/mL)                 0 2.5 5.0 10.0 15.0 20.0 25.0 50.0    ATO
                                                                                                    ATO+Ponatinib
                                                              Ponatinib(nmol/L)           DMSO    Ponatinib
                  D       DMSO       ATO          E                                F
                                                                   ***                             ***
                                                      150
                                                                 *   *** ***          (%)  40  ***  ***  ***  ***
                                                     Number of cloning  100            30
                                                              **
                                                                                       20
                        Ponatinib  ATO+Ponatinib       50                             Apoptosis ratio  10


                                                        0                               0
                                                          DMSO  ATO Ponatinib             DMSO  ATO Ponatinib
                                                                                                    ATO+Ponatinib
                                                                    ATO+Ponatinib


                   A,B:ATO(A)or ponatinib(B)effectively inhibited cell proliferation in a dose dependent manner. C-F:ATO combined with ponatinib synergistically
                                                                                                             *
                inhibited the viability of KG⁃1 cells(C),reduced the colony formation(D,E),and induced apoptosis(F)compared to the single drug treatment. P <
                   **
                          ***
                0.05,P < 0.01, P < 0.001(n=3).
                                       图1  ATO及普纳替尼对KG⁃1细胞增殖、集落形成及凋亡的影响
                       Figure 1 Effects of ATO and ponatinib on the proliferation,colony formation and apoptosis of KG⁃1 cells


                A                                B                  ***            C                ***
                                    ***
                                                                  **   *** ***           6      **  *  ***  ***
                    Relative mRNA expression  of Bcl⁃2  1.0  Relative mRNA expression  of Bax  6 4 2  Relative mRNA expression  of Caspase⁃3  4 2  **  *
                                 ***
                       1.5
                                                         8
                                                               **
                               ***
                       0.5

                         0
                           DMSO  ATO Ponatinib           0  DMSO  ATO Ponatinib          0  DMSO  ATO Ponatinib
                                                                                                     ATO+Ponatinib
                                                                     ATO+Ponatinib
                                     ATO+Ponatinib

                D                             ATO+Ponatinib
                                  DMSO  ATO  Ponatinib                                              Control
                                                                                          ***
                                                               Protein expression level  (Targets/GAPDH)  丈丈丈丈丈丈丈丈  * *  丈丈丈丈丈丈丈丈
                                                                         ***
                             Bax                 21 kDa            1.5   ***      ***     **  ***   ATO
                                                                                                    Ponatinib
                                                                                                  丈丈丈丈丈丈丈丈
                            Bcl⁃2                26 kDa            1.0  ** **     *      ** *** 丈丈丈丈丈丈丈丈  丈丈丈丈丈丈丈丈 ATO+Ponatinib
                                                                                             丈丈丈丈丈丈丈丈
                         Caspase⁃3               35 kDa            0.5      丈丈丈丈丈丈丈丈         丈丈丈丈丈丈丈丈
                                                                            丈丈丈丈丈丈丈丈
                                                                                             丈丈丈丈丈丈丈丈
                   Cleaved Caspase⁃3             17 kDa                     丈丈丈丈丈丈丈丈  丈丈丈丈丈丈丈丈  丈丈丈丈丈丈丈丈
                                                                            丈丈丈丈丈丈丈丈
                                                                                             丈丈丈丈丈丈丈丈
                                                                                    丈丈丈丈丈丈丈丈
                                                                            丈丈丈丈丈丈丈丈
                                                                                             丈丈丈丈丈丈丈丈
                          GAPDH                  36 kDa             0       丈丈丈丈丈丈丈丈  丈丈丈丈丈丈丈丈  丈丈丈丈丈丈丈丈
                                                                            丈丈丈丈丈丈丈丈
                                                                                    丈丈丈丈丈丈丈丈
                                                                         Bax     Bcl⁃2  Cleaved Caspase⁃3
                   A-C:ATO and ponatinib significantly inhibited Bcl⁃2(A)gene expression and promoted Bax(B)and Caspase⁃3(C)gene expression in KG⁃1
                                                                                                    ***
                                                                                              **
                                                                                       *
                cells. D:WesternblotanalysisofapoptoticproteinexpressionlevelinKG⁃1cellsafterATOandponatinibtreatment. P < 0.05,P < 0.01, P < 0.001(n=3).
                                      图2 ATO及普纳替尼对KG⁃1细胞凋亡基因、凋亡蛋白表达的影响
                     Figure 2 Effects of ATO and ponatinib on the expression of apoptosis⁃related genes and proteins in KG⁃1 cells
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