Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells

Liu, Shihai; Liu, Xiangping; Wang, Haibo; Zhou, Quan; Liang, Ye; Sui, Aihua; Yao, Ruyong; Zhao, Bin; Sun, Ming

doi:10.3892/or.2015.3872

Cited by 14 publications

(13 citation statements)

References 32 publications

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“…Despite the common use of Doxycycline as an antibiotic, there is some evidence of its antitumor activity, in particular, an inhibition of EMT and induction of apoptosis in different cancer types [12,32,33,34]. To date, there are no other data available on the possibility of overcoming GEM resistance with Doxycycline in other tumor models.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine

Varamo

Peraldo-Neia

Ostano

et al. 2019

Cancers

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Intrahepatic cholangiocarcinoma (ICC) is one of the most lethal liver cancers. Late diagnosis and chemotherapy resistance contribute to the scarce outfit and poor survival. Resistance mechanisms are still poorly understood. Here, we established a Gemcitabine (GEM) resistant model, the MT-CHC01R1.5 cell line, obtained by a GEM gradual exposure (up to 1.5 µM) of the sensitive counterpart, MT-CHC01. GEM resistance was irreversible, even at high doses. The in vitro and in vivo growth was slower than MT-CHC01, and no differences were highlighted in terms of migration and invasion. Drug prediction analysis suggested that Paclitaxel and Doxycycline might overcome GEM resistance. Indeed, in vitro MT-CHC01R1.5 growth was reduced by Paclitaxel and Doxycycline. Importantly, Doxycycline pretreatment at very low doses restored GEM sensitivity. To assess molecular mechanisms underlying the acquisition of GEM resistance, a detailed analysis of the transcriptome in MT-CHC01R1.5 cells versus the corresponding parental counterpart was performed. Transcriptomic analysis showed that most up-regulated genes were involved in cell cycle regulation and in the DNA related process, while most down-regulated genes were involved in the response to stimuli, xenobiotic metabolism, and angiogenesis. Furthermore, additional panels of drug resistance and epithelial to mesenchymal transition genes (n = 168) were tested by qRT-PCR and the expression of 20 genes was affected. Next, based on a comparison between qRT-PCR and microarray data, a list of up-regulated genes in MT-CHC01R1.5 was selected and further confirmed in a primary cell culture obtained from an ICC patient resistant to GEM. In conclusion, we characterized a new GEM resistance ICC model that could be exploited either to study alternative mechanisms of resistance or to explore new therapies.

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Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine

Varamo

Peraldo-Neia

Ostano

et al. 2019

Cancers

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“…Doxycycline has been shown to have high anti-metastatic activity and low cytotoxicity in melanoma and breast carcinoma [ 20 , 21 ]. In clinical trials with patients with pleural effusion, satisfactory results were achieved when doxycycline was used and there was inhibition of the activity of the suspended tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Doxycycline reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells

et al. 2015

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The gelatinase inhibitor doxycycline is the prototypical antitumor antibiotic. We investigated the effects of doxycycline on the migration, invasion, and metastasis of human lung cancer cell lines and in a mouse model. We also measured the effect of doxycycline on the transcription of epithelial-mesenchymal transition (EMT) markers, and used immunohistochemistry to determine whether EMT reversal was associated with doxycycline inhibition. Doxycycline dose-dependently inhibited proliferation, migration, and invasion of NCI-H446 human small cell lung cancer cells. It also suppressed tumor growth from NCI-H446 and A549 lung cancer cell xenografts without altering body weight, inhibited Lewis lung carcinoma cell migration, and prolonged survival. The activities of the transcription factors Twist1/2, SNAI1/2, AP1, NF-κB, and Stat3 were suppressed by doxycycline, which reversed EMT and inhibited signal transduction, thereby suppressing tumor growth and metastasis. Our data demonstrate functional targeting of transcription factors by doxycycline to reverse EMT and suppress tumor proliferation and metastasis. Thus, doxycycline selectively targets malignant tumors and reduces its metastatic potential with less cytotoxicity in lung cancer patients.

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“…Western blotting was based on previous protocols 19. The 1 × SDS buffer was used for lysate preparation, with the protein quantification via BCA Protein Assay (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

LncRNA MALAT1 acts as a miR-125a-3p sponge to regulate FOXM1 expression and promote hepatocellular carcinoma progression

Liu¹,

Qiu²,

He³

et al. 2019

J. Cancer

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Background: Hepatocellular carcinoma (HCC) is a prominent cancer type, with long non-coding RNAs (lncRNAs) being known to be relevant to its progression. We therefore investigated how a particular lncRNA known as the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was associated with HCC.Methods: Quantitative reverse transcriptase PCR (qPCR) was used to assess expression of MALAT1, Forkhead Box M1 (FOXM1) and miR-125a-3p in HCC tissue samples. How MALAT1 regulates HCC proliferation and metastasis was assessed through appropriate assays. FOXM1 was identified as a miR-125a-3p target using luciferase assays, and how MALAT1/miR-125a-3p alter FOXM1 expression was explored via qPCR and Western blotting.Results: HCC tissues exhibited MALAT1 upregulation. miR-125a-3p targeted FOXM1 and could be regulated by MALAT1. MALAT1 knockdown disrupted proliferation and invasion, whereas miR-125a-3p knockdown partially reversed this phenotype.Conclusions: These results indicate that MALAT1 modulates FOXM1 expression via being a miR-125a-3p sponge, thus promoting HCC progression.

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Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells

Cited by 14 publications

References 32 publications

Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine

Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine

Doxycycline reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells

LncRNA MALAT1 acts as a miR-125a-3p sponge to regulate FOXM1 expression and promote hepatocellular carcinoma progression

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