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. 2023 Apr 29;4(3):e236.
doi: 10.1002/mco2.236. eCollection 2023 Jun.

Synergistic augmentation of osimertinib-induced autophagic death by proguanil or rapamycin in bladder cancer

Di Xiao  1 , Simeng Xu  1 , Xiaochen Zhou  1 , Duo Li  1 , Mei Peng  1 , Xuetong Chu  1 , Zhirong Zhang  1 , Yan Peng  1 , Alex F Chen  1   2 , Xiaoping Yang  1   3
Affiliations

Synergistic augmentation of osimertinib-induced autophagic death by proguanil or rapamycin in bladder cancer

Di Xiao et al. MedComm (2020). .
No abstract available

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Autophagy induced by proguanil or rapamycin enhances antitumor effect of osimertinib in bladder cancer. (A) The effect of osimertinib (Osi) inhibiting T24 proliferation was evaluated using colony formation assay. Above: The full view of wells was taken through stereomicroscope. Below: A representative image of the well was taken through an inverted microscope. (B) T24 were treated with osimertinib for 24 h, and the expression of total or phosphorylated EGFR, AKT, and ERK were measured by Western blot. (C) T24 were treated with osimertinib for 24 h, and the expression of p62, Beclin‐1, and LC3 was measured by Western blot. (D) T24 were treated with osimertinib (2 μM) or proguanil (10 μM) for 24 h. Subsequently, cells are then fixed with electron microscope fixative and observed under a transmission electron microscope (red arrows indicate autophagosomes). (E) T24 were co‐treated with 5 μM CQ, 2 mM NH4Cl or 5 mM 3MA, and 4 μM osimertinib for 72 h, and the cell viability was measured by MTT. (F) T24 were treated with osimertinib (1 μM) and proguanil (5 μM) alone or in combination, and the cell viability was measured by colony formation assay. Above: The full view of wells was taken through stereomicroscope. Below: A representative image of the well was taken through an inverted microscope. (G) T24 were treated with osimertinib (2 μM) and proguanil (10 μM) for 24 h, and the expression of p62, Beclin‐1, and LC3 was measured by Western blot. (H) The picture of xenograft tumors treated with osimertinib and proguanil were taken after mice were treated for 14 days. (I) Weights of tumors treated with osimertinib and proguanil were measured after 14 days of administration. (J) Western blot analysis of the expression of P62, Beclin‐1, and LC3 in tumor tissues treated with osimertinib and proguanil. (K) T24 cells were treated with osimertinib (1 μM) and rapamycin (0.1 μM) alone or in combination, and the cell viability was measured by colony formation assay. Above: The full view of wells was taken through stereomicroscope. Below: A representative image of the well was taken through an inverted microscope. (L) T24 was treated with osimertinib (2 μM) and rapamycin (0.2 μM) for 24 h, and the expression of p62, Beclin‐1, and LC3 was measured by Western blot. (M) The picture of xenograft tumors treated with osimertinib and rapamycin was taken after mice were treated for 14 days. (N) Weights of tumors treated with osimertinib and rapamycin were measured after 14 days of administration. (O) Western blot analysis of the expression of p62, Beclin‐1, and LC3 in tumor tissues treated with osimertinib and rapamycin. (P) Graphical abstract showed that proguanil or rapamycin enhanced the sensitivity of BC cells to osimertinib. The graphical abstract was designed using the software of Adobe Illustrator CS6. Error bars represent means ± SD from triplicate experiments. Materials and methods are included in Supporting Information (*p < 0.05, **p < 0.01, ***p < 0.001, # p < 0.05, ## p < 0.01, ### p < 0.001).
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