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第45卷第9期           张  鸽,陈 昕,顾婧瑶,等. circ_0003633对肺腺癌细胞奥希替尼耐药的作用研究[J].
                  2025年9月                     南京医科大学学报(自然科学版),2025,45(9):1229-1241                      ·1239 ·


                                  A            HCC827/OR                           H1975/OR
                                        1.5                                 1.5
                                                  **                               **  **
                                     Relative expression  of ALDOC  1.0  Relative expression  of ALDOC  1.0
                                                **


                                        0.5
                                                                            0.5
                                         0                                   0
                                                                               si⁃ALDOC⁃1#
                                            si⁃ALDOC⁃1#
                                            si⁃NC  si⁃ALDOC⁃2#                 si⁃NC  si⁃ALDOC⁃2#

                B
                            HCC827/OR                                       H1975/OR
                   1.2                      si⁃NC                  2.0                      si⁃NC
                   1.0              **      si⁃ALDOC                                    **  si⁃ALDOC
                  nm)  0.8     **           si⁃NC+1.0 μmol/L Osimertinib  nm)  1.5          si⁃NC+1.0 μmol/L Osimertinib
                                                                                            si⁃ALDOC+1.0 μmol/L
                                            si⁃ALDOC+1.0 μmol/L
                  (450  0.6                 Osimertinib           (450  1.0        **       Osimertinib
                   0.4
                                                                  D
                  D
                                                                   0.5
                   0.2
                    0                                              0.0
                      0   24   48   72  96                           0    24   48   72  96
                         Incubation time(h)                              Incubation time(h)
                  C
                                 HCC827/OR                   H1975/OR
                                                                                         si⁃NC
                            si⁃NC       si⁃ALDOC        si⁃NC      si⁃ALDOC              si⁃ALDOC
                                                                                         si⁃NC+1.0 μmol/L Osimertinib
                       μmol/L                                                       150  **  *
                                                                                         si⁃ALDOC+1.0 μmol/L Osimertinib
                       0                                                            100      **     *  * *
                     Osimertinib                                                   Number of colonies

                       1.0 μmol/L                                                   50


                                                                                     0
                                                                                        HCC827/OR  H1975/OR


                D               HCC827/OR                      H1975/OR                   si⁃NC
                                                                                          si⁃ALDOC
                          si⁃NC         si⁃ALDOC         si⁃NC         si⁃ALDOC
                                                                                          si⁃NC+1.0 μmol/L Osimertinib
                                                                                          si⁃ALDOC+1.0 μmol/L Osimertinib
                    μmol/L                                                           300   **  * **
                  Osimertinib  0                                                     Number of cells  200  **  * **

                    1.0 μmol/L                                                       100



                                                                                       0
                                                                                         HCC827/OR   H1975/OR
                   A:Validation of ALDOC knockdown efficiency via qRT⁃PCR. B,C:CCK⁃8 and colony formation assay demonstrated attenuated proliferative ca⁃
                pacity in ALDOC⁃knockdown drug⁃resistant cells. D,E:Transwell migration assay revealed diminished migratory potential of ALDOC⁃depleted drug⁃re⁃
                                 **
                        *
                sistant cells. P < 0.05 and P < 0.01(n=3).
                                                 图9   ALDOC促进耐药细胞增殖迁移
                                 Figure 9  ALDOC promoted the proliferation and migration of drug⁃resistant cells
                号通路参与耐药发生。                                        制是 circ_0003633 与 hnRNPA1 结合促进 ALDOC 的
                    综上所述,circ_0003633促进了肺腺癌奥希替尼                   表达,并激活 PI3K/AKT 信号通路,这将为逆转奥希
                耐药细胞的增殖、迁移及耐药,其发挥作用的可能机                           替尼耐药提供新的靶点。
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