Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer

Feng, Haoran; Cheng, Xi; Kuang, Jie; Chen, Lingxie; Yuen, Stanley; Shi, Minmin; Liang, Juyong; Shen, Baiyong; Jin, Zhijian; Yan, Jiqi; Qiu, Weihua

doi:10.1038/s41419-018-1054-3

Cited by 110 publications

(104 citation statements)

References 50 publications

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“…In the present study, the combination of PLB and CDDP treatment induced autophagy, as evidenced by the accumulation of AVOs and autophagosomes as well as the upregulation of LC3-II, etc. The AKT/mTOR signaling pathway plays a key regulatory role in cell functions such as cell growth, apoptosis, and autophagy [39]. Our results showed that the PLB and CDDP cotreatment significantly inhibited the expression of p-AKT and p-mTOR, compared with either PLB and CDDP treatment alone.…”

mentioning

confidence: 55%

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Xue

Pan

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.

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confidence: 55%

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Xue

Pan

Zhou

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Feng H et al con rmed that Akt/mTOR signaling pathway participate in the inhibition of autophagy and apoptosis at the same time 22 . Huo JF et al con rmed that the overexpression of GAS5 can enhance the cell sensitivity to cisplatin by inhibiting the excessive autophagy and this effect is achieved by regulating the expression of mTOR 23 . In the present study,the results showed that the level of miR-144 decreased,the level of mTOR increased and the autophagy level decreased after up-regulating the expression of GAS5, while the level of autophagy increased after upregulating GAS5 and adding mTOR inhibitor GDC-0349, suggesting that GDC-0349 can reverse the inhibition effect of GAS5 on autophagy after up regulating mTOR.…”

Section: Discussionmentioning

confidence: 99%

Expression of Long-Chain Noncoding RNA GAS5 in Osteoarthritis And Its Effect on Apoptosis And Autophagy of Osteoarthritis Chondrocytes

Qiao

Liu

et al. 2020

Preprint

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Objective: To investigate the expression of long chain non-coding RNA GAS5 in osteoarthritis(OA) and the effect on autophagy and apoptosis of chondrocytes. Method: OA rat model was constructed and the expressions of GAS5 in articular cartilage tissues at 4 weeks(early OA) and 12 weeks(late OA) after modeling were detected. The chondrocytes of OA rat were isolated, cultured and transfected with si-GAS5 to silence the GAS5. Then the change of apoptosis and autophagy levels of OA chondrocytes were detected. The microRNA binding to GAS5 and the competitive target gene were analyzed and verified. Results: The expression of GAS5 in cartilage tissue of OA rats was higher than that of control, which was higher in late OA than that in early OA. After silencing the GAS5, the autophagy ability of OA chondrocytes was increased and the apoptosis rate was decreased. GAS5 could bind with miR-144 competitively and regulate mTOR positively. The mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on cell autophagy but could not reverse the promotion on apoptosis. Conclusion: GAS5 expression was high and increased with the progression of OA. GAS5 could inhibit the autophagy and promote the apoptosis of OA chondrocytes, and the effect on autophagy may be related to the regulation on mTOR.

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“…Phosphorylation of mTOR and Akt is a key signaling step for the initiation of autophagy (30,31). To gain an insight into the signaling for BZA-induced autophagy, we determined the phosphorylation of mTOR, Akt, ULK, AMPK, and STAT3.…”

Section: Bza-induced Autophagy Is Associated With Ros Production Andmentioning

confidence: 99%

Bazedoxifene Suppresses Intracellular Mycobacterium tuberculosis Growth by Enhancing Autophagy

Ouyang

Zhang

Lin

et al. 2020

mSphere

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Tuberculosis (TB) is still the leading killer caused by Mycobacterium tuberculosis infection. There is a clear need for new treatment strategy against TB. It has been reported that tamoxifen, known as a selective estrogen receptor modulator (SERM), exhibits antimycobacterial activity and inhibits M. tuberculosis growth in macrophages. However, it remains unknown whether such antimicrobial activity is a general property of all SERMs and how it works. In this study, we identified that bazedoxifene (BZA), a newer SERM, inhibits intracellular M. tuberculosis growth in macrophages. BZA treatment increases autophagosome formation and LC3B-II protein expression in M. tuberculosis-infected macrophages. We further demonstrated that the enhancement of autophagy by BZA is dependent on increased reactive oxygen species (ROS) production and associated with phosphorylation of Akt/mTOR signaling. In summary, our data reveal a previously unappreciated antimicrobial function of BZA and suggest that future investigation focusing on the mechanism of action of SERMs in macrophages may lead to new host-directed therapies against TB. IMPORTANCE Since current strategies for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have low efficacy and highly negative side effects, research on new treatments including novel drugs is essential for curing drug-resistant tuberculosis. Host-directed therapy (HDT) has become a promising idea to modulate host cell responses to enhance protective immunity against pathogens. Bazedoxifene (BZA), which belongs to a new generation of SERMs, shows the ability to inhibit the growth of M. tuberculosis in macrophages and is associated with autophagy. Our findings reveal a previously unrecognized antibacterial function of BZA. We propose that the mechanism of SERMs action in macrophages may provide a new potential measure for host-directed therapies against TB.

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Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer

Cited by 110 publications

References 50 publications

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

Expression of Long-Chain Noncoding RNA GAS5 in Osteoarthritis And Its Effect on Apoptosis And Autophagy of Osteoarthritis Chondrocytes

Bazedoxifene Suppresses Intracellular Mycobacterium tuberculosis Growth by Enhancing Autophagy

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