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·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

