Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells

Kojima, Yasutaka; Otsuki, Naoki; Kubo, Mie; Kitamoto, Junko; Takata, Eri; Saito, Hiroki; Kosaka, Kyoko; Morishita, Naoya; Uehara, Natsumi; Shirakawa, Toshiro; Nibu, Ken-Ich

doi:10.1038/s41417-018-0024-3

Cited by 11 publications

(6 citation statements)

References 18 publications

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“…Gene therapy has become a worthwhile supplement to current oral carcinoma treatment, including viral and non-viral based therapy. 30 Effective therapeutic targets and appropriate gene delivery vectors represent two crucial issues in oral carcinoma gene therapy studies. In the present study, we used an hBimS gene encoding plasmid delivered by a non-viral gene vector DMP cationic micelles (Scheme 1).…”

Section: Discussionmentioning

confidence: 99%

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

Ma¹,

Li²,

Jin³

et al. 2022

IJN

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Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with more than 300,000 new cases annually. Despite advances in existing treatments, including surgery, radiation, chemotherapy, and immunotherapy, the overall survival and prognosis have remained poor. However, gene therapy based on non-viral vectors provides new ideas for the treatment of OSCC. Here, we aimed to prepare and describe the synthesis, biosafety, and preclinical efficacy of DOTAP-mPEG-PCL (DMP) in OSCC gene therapy. Methods: We prepared a nano-sized hybrid cationic micelle DMP. DMP micelles were prepared by self-assembling cationic lipid DOTAP and mPEG-PCL polymer. We evaluated the characteristics of this cationic micelle in vitro. Combined with encoding the apoptosis-inducing BimS gene, we established the DMP/phBimS complex and evaluated its anti-tumor effect in vitro. We also established a mouse tongue xenograft model to evaluate the antitumor effect of the DMP/phBimS complex in vivo through local and systemic administration prospectively. Results:The DMP cationic micelle is spherical in shape, with an average diameter of 28.32 ± 3.56 nm and an average zeta potential of 43.43 ± 0.82 mV. By activation of lipid raft-mediated endocytosis caveolin-mediated endocytosis, DMP could efficiently deliver plasmid into SCC15 cells (efficiency: 52.07% ± 1.63%), with an ideal biosecurity. When loaded by plasmid encoding the apoptosisinducing BimS gene, the DMP/phBimS complex exhibited an obvious anti-proliferation effect of SCC15 in vitro through the apoptosis pathway (33.9% ± 2.62% apoptosis rate). By local administration, the DMP/phBimS complex showed ideal anti-tumor properties in the nude mouse tongue xenograft model, with an average tumor inhibition rate of 65.66%. Furthermore, through systematic administration, the DMP/phBimS complex obviously inhibited OSCC growth, with an average inhibition rate of 45.63% (DMP/ phBimS) and an appropriate biocompatibility. Conclusion:The DMP/phBimS complex is an optional effective option for suicide gene therapy for OSCC.

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Section: Discussionmentioning

confidence: 99%

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

Ma¹,

Li²,

Jin³

et al. 2022

IJN

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“…In addition, HPV-positive patients and HPV-negative patients have different responses to treatment and prognosis. 17 HPV-positive patients have more obvious effects on radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

<p>DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1</p>

Zhang¹,

Mi²,

Deng³

et al. 2020

OTT

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Introduction: Head and neck squamous cell carcinoma (HNSCC), which rank the 7th malignant tumors worldwide, is closely related to methylation and HPV infection. Ionizing radiation therapy is the main strategy for HNSCC patients in advanced stage. Previously, HPV-positive HNSCC predict better prognosis than HPV-negative HNSCCs under radiotherapy, however its molecular mechanism is unresolved. SMG1 serves as a potential tumor suppressor in various cancers, including HNSCC. Methods: The mRNAs and proteins expression of HPV E6/E7, p16, p53, DNMT1, SMG1 were detected after different treatments by qPCR and Western blot. The clone formation ability was measured in radiation dose after different treatments. Results: In our study, the expression of HPV16 E6, DNA Methyltransferase 1(DNMT1) and SMG1 in head and neck carcinomas cell lines was detected by RT-qPCR and Western blot. Forced E6 level in HPV-negative cells by overexpression plasmid promoted the expression of DNMT1, which resulted in decreased SMG1 expression. Silenced SMG1 in HPV-negative HNSCC cells elicited increased radiation sensitivity, suggesting that SMG1 may be an effective switch to regulate the effect of radiotherapy in HNSCC. Conclusion: Our study indicated that DNMT1 enhances the radiosensitivity of HPVpositive head and neck squamous cell carcinomas via downregulating SMG1.

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“…Thus, it remains unclear whether the E6 protein is expressed in clinical specimens and cell lines. As for the E7 protein, a previous study showed E7 protein expression in UM47 by western blotting using M-PER as a lysis buffer 19 . We performed western blotting with M-PER in the same conditions as with sample buffer, but E7 protein could not be detected in both condition (Fig.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of HPV16 E7 expression in head and neck carcinoma cell lines and clinical specimens

Kitamura

Nimura

Ito

et al. 2020

Sci Rep

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Human papillomavirus (HPV) 16 infection in the oropharynx is one of the major risk factors for oropharyngeal carcinoma. Although the HPV E6 and E7 proteins are known to have a role in head and neck carcinogenesis, whether their expression is maintained once the tumour has developed still remains unclear. We evaluated the expression of these proteins in HPV16-positive cancer cell lines and clinical oropharyngeal specimens. Two out of the four commercially available antibodies directed against the E7 protein could detect the E7 protein overexpressed in the 293FT cells, human embryonic kidney cells, although none of the four commercially available anti-E6 antibodies could detect the overexpressed E6 protein. Whereas HPV16-positive head and neck or cervical carcinoma cell lines expressed the E7 mRNA, the antibodies with an ability to detect the E7 protein could not detect it in western blotting in these HPV16-positive cell lines. In clinical specimens, E7 protein was partially detected in p16-positive area in p16-positive and HPV16 DNA-positive samples, but not in p16-negative and HPV DNA-negative or p16-positive and HPV DNA-negative samples. Consistent with these findings, the E7 protein was poorly translated from the endogenous structure of the E7 mRNA, although significant E7 mRNA expression was detected in these samples. Our findings indicate that E7 protein is partially expressed in p16-positive area in p16-positive and HPV16 DNA-positive clinical specimens.

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Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells

Cited by 11 publications

References 18 publications

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

<p>DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1</p>

Evaluation of HPV16 E7 expression in head and neck carcinoma cell lines and clinical specimens

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