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第45卷第9期
               ·1234 ·                           南 京    医 科 大 学 学         报                        2025年9月


                                                                中 [15] 。靶向 EGFR 突变的小分子 EGFR⁃TKI 改善了
              3  讨 论
                                                                这些患者的预后和治疗结果。奥希替尼是一种不
                  EGFR突变存在于40%~60%的东亚LUAD患者                     可 逆 的 第 3 代 EGFR ⁃ TKI,已 被 批 准 用 于 EGFR

                A                              B
                          si⁃NC                    100                             100   HCC827/OR si⁃circ0003633
                     1.5                                    HCC827/OR si⁃NC
                          si⁃circ0003633⁃1#        (%)  80                        (%)  80
                  Relative expression  of cirrc_0003633  1.0  **  Cell viability  60  IC50=4.758 μmol/L  Cell viability  60  IC50=2.860 μmol/L
                          si⁃circ0003633⁃2#
                                                                                   40
                                                    40
                                                    20
                                                                                   20
                     0.5
                                      **
                              **
                            **
                                                     0
                                                      00   0.5  1.0  1.5  2.0       0 00  0.5  1.0  1.5  2.0
                       0                            Osimertinib concentation[lg(μmol/L)]  Osimertinib concentation[lg(μmol/L)]
                         HCC827/OR  H1975/OR
                       C          HCC827/OR                                   H1975/OR
                               si⁃NC                                       si⁃NC
                               si⁃circ_0003633                             si⁃circ_0003633
                           4   si⁃NC+1.0 μmol/L Osimertinib            4   si⁃NC+1.0 μmol/L Osimertinib
                               si⁃circ_0003633+1.0 μmol/L Osimertinib      si⁃circ_0003633+1.0 μmol/L Osimertinib
                          nm)  3                **                    nm)  3               **
                          (450  2           **  **                    (450  2     **   **
                          D
                           1              **                          D  1                 **
                                                                                      **
                                      **                                         **
                           0                                           0
                            0    24   48  72   96                       0   24   48   72   96
                                Incubation time(h)                          Incubation time(h)
               D              HCC827/OR                  H1975/OR
                                                                                    si⁃NC
                         si⁃NC     si⁃circ_0003633  si⁃NC     si⁃circ_0003633       si⁃circ_0003633
                                                                                    si⁃NC+1.0 μmol/L Osimertinib
                    μmol/L                                                     250  **  *      *  **
                                                                                    si⁃circ_0003633+1.0 μmol/L Osimertinib
                    0                                                          200      **         *
                  Osimertinib                                                 Number of colonies  150

                                                                               100
                    1.0 μmol/L                                                 50

                                                                                0
                                                                                   HCC827/OR  H1975/OR

                                                                                           si⁃NC
               E                HCC827/OR                       H1975/OR                   si⁃circ_0003633
                           si⁃NC       si⁃circ_0003633    si⁃NC      si⁃circ_0003633       si⁃NC+1.0 μmol/L Osimertinib
                                                                                           si⁃circ_0003633+1.0 μmol/L
                                                                                      200  Osimertinib
                    μmol/L                                                            150   *  *      *  **
                  Osimertinib  0                                                     Number of cells  100  **  *

                    1.0 μmol/L                                                         50


                                                                                        0
                                                                                          HCC827/OR  H1975/OR
                 A:qRT⁃PCR was used to detect the knockdown efficiency of circ_0003633. B:The IC50 value changed after knockdown of circ_0003633. C,D:CCK⁃8
              and colony formation assays indicated that the proliferation ability of cells decreased after knockdown of circ_0003633. E:The migration ability of cells
                                           *
                                                 **
              decreased after knockdown of circ_0003633. P < 0.05,P < 0.01(n=3).
                              图3 敲低circ_0003633后对奥希替尼耐药细胞增殖、迁移及奥希替尼敏感性的影响
              Figure 3  The effect of knockdown of circ_0003633 on the proliferation,migration and osimertinib sensitivity of osimertinib⁃
                      resistant cells
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