HUI CAO,Shili Wang,Yaohui Liu. Antitumor and vascular effects of apatinib combined with chemotherapy in mice with non-small-cell lung cancer. Oncol Transl Med, 2021, 7: 141-147.
Antitumor and vascular effects of apatinib combined with chemotherapy in mice with non-small-cell lung cancer
Received:November 03, 2020  Revised:June 22, 2021
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KeyWord:non-small-cell lung cancer (NSCLC); apatinib; pemetrexed
Author NameAffiliationE-mail
HUI CAO Department of Pharmacy, Zigong Fourth People''s Hospital, Zigong 643000, China benbenda3321@163.com 
Shili Wang Department of Pharmacy, Zigong Fourth People''s Hospital, Zigong 643000, China  
Yaohui Liu Department of Pharmacy, Zigong First People''s Hospital, Zigong 643000, China  
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Abstract:
      Objective The aim of this study was to investigate the antitumor and vascular effects of apatinib use combined with chemotherapy on mice with non-small-cell lung cancer (NSCLC). Methods First, 60 tumor-bearing nude mice were randomly divided into control, low-dose, and high-dose groups. Four nude mice per group were sacrificed before administration and on days 1, 3, 7, and 10 after administration. HIF-1α expression in tumor tissues was detected. Second, 32 nude mice were randomly divided into control, premetrexed, synchronous, and sequential groups. The weights and tumor volumes of mice were recorded. Results (1) HIF-1α expression decreased significantly on days 3 and 7 after low-dose apatinib treatment. There was no significant difference in HIF-1α expression in the high-dose apatinib group (P > 0.05). MMP- 2 and MMP-9 expression levels in the low-dose apatinib group were significantly lower than those in the control group (P < 0.05). (2) In the low-dose apatinib group, the microvessel density increased gradually from days 3 to 7 post-treatment, while that in the high-dose apatinib group decreased significantly. (3) The inhibitory effect of sequential therapy using low-dose apatinib and pemetrexed was optimal, while that of synchronous treatment was not better than that of pemetrexed usage alone. Sequential treatment using low-dose apatinib and pemetrexed exerted the best antitumor effect. (4) The expression levels of p-AKT, p-mTOR, p-MEK, and p-ERK in the sequential group were significantly lower than those in the other three groups (P < 0.05). Conclusion Apatinib usage involves certain considerations, such as dose requirements and time window for vascular normalization during lung cancer treatment in nude mice, suggesting that dynamic contrastenhanced magnetic resonance imaging and other tests can be conducted to determine the vascular normalization window in patients with lung cancer and to achieve the optimal anti-vascular effect.
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