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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2023 07

Page:

1212-1217

Research Field:

Publishing date:

Info

Title:

Inhibitory effect of JNJ-26481585 on pemetrexed resistant xenotransplanted tumor of human lung adenocarcinoma in nude mice and its mechanism

Author(s):

LI Qi; ZHAO Min; HU Dandan; QIN Junjiao

Department of Respiratory Medicine,Affiliated Puren Hospital of Wuhan University of Science and Technology,Hubei Wuhan 430081,China.

Keywords:

JNJ-26481585; FAM96A; Bcl-2; pemetrexed; drug resistance; lung neoplasms

PACS:

R73-3

DOI:

10.3969/j.issn.1672-4992.2023.07.006

Abstract:

Objective:To investigate the inhibitory effect and anticancer mechanism of JNJ-26481585 on pemetrexed resistant xenotransplanted tumor of human lung adenocarcinoma in nude mice.Methods£ºThe xenograft tumor nude mouse models of human lung adenocarcinoma A549/pemetrexed resistant cells(A549/PEM) were established and randomly divided into model group,pemetrexed group,JNJ group and combined group(pemetrexed+JNJ).The nude mice were sacrificed at the end of the treatment observation on the 28th day,and the tumor tissue samples were moved for testing.The tumor volume and body weight of four groups of nude mice were measured.The tumor inhibition rate was calculated,and the toxic and side effects of drugs in each treatment group on nude mice bearing tumor were observed.TUNEL method was used to detect the difference of apoptosis of transplanted tumor cells.qRT-PCR was used to detect the difference of gene mRNA expression of FAM96A,Bax and Bcl-2 in the four groups,and Western blot was used to detect the difference of protein expression of FAM96A,Bax and Bcl-2 in the four groups.Results£ºThe tumor volume and body weight of the combined group were lower than those of the JNJ group.The tumor volume and body weight of the JNJ group were lower than those of the pemetrexed group.The tumor inhibition rate of the combined group was higher than that of the JNJ group,and the tumor inhibition rate of the JNJ group was higher than that of the pemetrexed group(all P<0.05).The apoptosis rate of combined group was higher than that of JNJ group,and that of JNJ group was higher than that of pemetrexed group(all P<0.05).The expression levels of FAM96A and Bax in combined group were higher than those in JNJ group.The expression levels of FAM96A and Bax in JNJ group were higher than those in pemetrexed group.The expression level of Bcl-2 in combined group was lower than that in JNJ group,and the expression of Bcl-2 in JNJ group was lower than that in pemetrexed group(all P<0.05).Compared with the single drug group,the blood cell count decreased significantly and the indexes of liver function increased significantly in the combined group(P<0.05).There was no significant difference in blood cells and liver function between pemetrexed group and JNJ group(P<0.05).Conclusion£ºJNJ-26481585 can promote cancer cell apoptosis by activating the expression of tumor suppressor gene FAM96A,up regulating the expression of Bax and down regulating the expression of Bcl-2,reverse the drug resistance of lung adenocarcinoma to pemetrexed,and play an anticancer role in synergy with pemetrexed.

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Last Update: 2023-02-28