Pyroptosis is involved in the inhibitory effect of FL118 on growth and metastasis in colorectal cancer
Authors: Xiaoyi Zhang
Lixia Ji
Guohui Jiang
Mei Han
Jing Xie
Zhenxue Tang
Hui Gao
Zhihong Yang
Quanzhong Su
Feng Zhong
Zhantao Liu
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colorectal cancer; FL118; Growth; Inflammatory response; Metastasis
Affiliations: Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China., School of Basic Medicine, Qingdao University, Qingdao 266021, China., School of Public Health, Qingdao University, Qingdao 266021, China., Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China. Electronic address: ., Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China; Zhaoqing Yikai International Pharmaceutical Research Institute, Zhaoqing 526070, China. Electronic address: .

Abstract:  Aims: Pyroptosis is a newly discovered inflammatory programmed cell death. This study was to investigate whether pyroptosis is involved in the anti-colorectal cancer process of FL118. Materials and methods: The relationship between NLRP3 and caspase-1 and colorectal cancer was analyzed by bioinformatics. MTT was used to detect the cell viability. Cell membrane integrity was examined by LDH release. Wound healing assay and Transwell were used to detect the cell migration and invasion respectively. TUNEL was to check the cell death. The expression of pyroptosis-related factors was detected using qRT-PCR, Western blotting, Immunofluorescence and Elisa. And H&amp;E staining was used to detect the toxicity of FL118 in colorectal cancer. Key findings: In vitro, FL118 significantly inhibited the proliferation, migration and invasion of colorectal cancer, and the morphological characteristics of pyroptosis were observed under the microscope. With the change of FL118 concentration, the release rate of LDH in the supernatant and the expression of pyroptosis-related factors emerged an increase. However, pyroptosis induced by FL118 was reversed with the participation of MCC950 and VX-765, which suppressed the antitumor effect of FL118. In vivo, the result in the xenograft animal model and lung metastasis model experimental showed that FL118 could activate pyroptosis and thus inhibit the metastasis of colorectal cancer. Significance: FL118 restrains the growth and metastasis of colorectal cancer by inducing NLRP3-ASC-Caspase-1 mediated pyroptosis, which provides important evidence in the study on the role of pyroptosis and different tumors. 

Retracted: No

PubPeer comments:
 Two images have been reused between Figure 2D and Figure 7C (please see attached image). For the sake of clarity, I provide both the original version of panel 7C (the duplication in the area marked in blue is best visible here) as well as a version of panel 7C flipped by 90 degrees (the duplication in the area marked in red is best visible here). Could the authors comment? ![file] , 
 Dear Sir Madam, @Pubpeer Thank you very much for your questions, which have attracted our attention.We apologize to you for the inconvenience .We studied the problem carefully and looked up all the original records related to all experiments. Although our experimental results support the conclusion of this paper, we are sorry that we have confused these graphs. Specifically, we misused the similar figures in Figure 7C and Figure 2D. Since the experimental results of VX-765 group were similar to those of the control group and multiple images were taken in one field of view at a time, we did not observe this error when selecting images from multiple images taken after the experiment. The revised Figure 7C is as follows. We sincerely apologize for the unintentional mistakes made before the submission. In the submission and subsequent review and publication procedures, we are sorry that we did not find them in time which caused problems for peers. Once again, we sincerely thank peers for the questions , so that our articles can be more rigorous and credible. We insist on the quality of the experiment and the conclusion of the paper. We will immediately contact the editorial department of Life Sciences to solve the problem as soon as possible. Fig.7C ![file] ,