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第45卷第9期
               ·1236 ·                           南 京    医 科 大 学 学         报                        2025年9月


              T790M 阳性且既往 EGFR⁃TKI 进展的患者             [16] 。此    出良好疗效。然而,获得性耐药的出现是不可避免
              外,奥希替尼作为 EGFR 突变的晚期非小细胞肺癌                         的 [17] ,而耐药机制尚未完全阐明,因此了解奥希替
             (non⁃small cell lung cancer,NSCLC)的一线治疗显示          尼获得性耐药的机制具有重要意义。

                A                                                       B
                      1.5    HCC827/OR          1.5    H1975/OR                     H1975/OR  HCC827/OR
                                                          *
                                 *
                   Relative expression  of hnRNPA1  1.0  Relative expression  of hnRNPA1  1.0  si⁃NC  si⁃hnRNPA1⁃1#  si⁃hnRNPA1⁃2#  si⁃NC  si⁃hnRNPA1⁃1#  si⁃hnRNPA1⁃2#
                              *
                                                        *
                      0.5
                                                0.5
                       0                         0                        hnRNPA1                       34 kDa
                                                       si⁃hnRNPA1⁃2#
                             si⁃hnRNPA1⁃2#
                                                    si⁃NC
                         si⁃hnRNPA1⁃1#            si⁃hnRNPA1⁃1#             β⁃actin                     42 kDa
                          si⁃NC
              C           HCC827/OR                                        H1975/OR
                                           si⁃NC                                       **  si⁃NC
                 1.2                                             1.5
                                       **  si⁃hnRNPA1                                      si⁃hnRNPA1
                                  **                                              **
                 1.0                       si⁃NC+1.0 μmol/L Osimertinib                    si⁃NC+1.0 μmol/L Osimertinib
                nm)  0.8     **            si⁃hnRNPA1+1.0 μmol/L  nm)  1.0                 si⁃hnRNPA1+1.0 μmol/L
                                                                                           Osimertinib
                                           Osimertinib
                (450  D  0.6                                     (450  D  0.5
                 0.4
                 0.2
                  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⁃hnRNPA1       si⁃NC     si⁃hnRNPA1
                                                                                     si⁃hnRNPA1
                                                                                     si⁃NC+1.0 μmol/L Osimertinib
                    μmol/L                                                      250  si⁃hnRNPA1+1.0 μmol/L Osimertinib
                    0                                                           200  **  * **
                  Osimertinib                                                  Number of colonies  150  **  * **
                                                                                100
                    1.0 μmol/L                                                   50 0  HCC827/OR  H1975/OR






              E                HCC827/OR                      H1975/OR                     si⁃NC
                                                                                           si⁃hnRNPA1
                         si⁃NC        si⁃hnRNPA1        si⁃NC        si⁃hnRNPA1
                                                                                           si⁃NC+1.0 μmol/L Osimertinib
                                                                                     300   si⁃hnRNPA1+1.0 μmol/L
                   μmol/L                                                                  * Osimertinib  *  *
                                                                                              *
                 Osimertinib  0                                                     Number of cells  200  **  **

                   1.0 μmol/L
                                                                                     100
                                                                                       0
                                                                                         HCC827/OR  H1975/OR
                 A:qRT⁃PCR was used to detect the knockdown efficiency of hnRNA1. B:Western blot was employed to assess the knockdown efficiency of hnRNA1.
              C,D:The results of CCK8 and colony formation assays indicated that the proliferation ability of drug⁃resistant cells decreased after knockdown of hnRN⁃
                                                                                           *
                                                                                                    **
              PA1. E:The Transwell assay showed that the migration ability of drug⁃resistant cells declined after knockdown of hnRNPA1. P < 0.05 and P < 0.01(n=3).
                                               图6 hnRNPA1促进耐药细胞增殖迁移
                              Figure 6  hnRNPA1 promoted the proliferation and migration of drug⁃resistant cells
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