scholarly journals A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 681
Author(s):  
Xiaoli Liu ◽  
Huichao Lin ◽  
Jiaao Song ◽  
Taiyi Zhang ◽  
Xiaoying Wang ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Viability ◽  
Cellular Damage ◽  
Rapid Screening ◽  
Cancer Drug ◽  
Biological Research ◽  
Dead Cell ◽  
Spheroid Formation ◽  
Cellular Spheroids ◽  
Anti Cancer

Cell culture is important for the rapid screening of anti-cancer drug candidates, attracting intense interest. Traditional 2D cell culture has been widely utilized in cancer biological research. However, 3D cellular spheroids are able to recapitulate the in vivo microenvironment of tissues or tumors. Thus far, several 3D cell culture methods have been developed, for instance, the hanging drop method, spinner flasks and micropatterned plates. Nevertheless, these methods have been reported to have some disadvantages, for example, medium replacement is inconvenient or causes cellular damage. Here, we report on an easy-to-operate and useful micro-hole culture chip (SimpleDrop) for 3D cellular spheroid formation and culture and drug analysis, which has advantages over the traditional method in terms of its ease of operation, lack of shear force and environmentally friendliness. On this chip, we observed the formation of a 3D spheroid clearly. Three drugs (paclitaxel, cisplatin and methotrexate) were tested by both cell viability assay and drug-induced apoptotic assay. The results show that the three drugs present a similar conclusion: cell viability decreased over time and concentration. Moreover, the apoptotic experiment showed a similar trend to the live/dead cell assay, in that the fraction of the apoptotic and necrotic cells correlated with the concentration and time. All these results prove that our SimpleDrop method is a useful and easy method for the formation of 3D cellular spheroids, which shows its potential for both cell–cell interaction research, tissue engineering and anticancer drug screening.

Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation

2016 ◽  
Vol 77 ◽  
pp. 164-173 ◽  
Author(s):  
Shangquan Wu ◽  
Xiaoli Liu ◽  
Xiarong Zhou ◽  
Xin M. Liang ◽  
Dayong Gao ◽  
...  
Keyword(s):  
Cell Viability ◽  
Rapid Screening ◽  
Cancer Drug ◽  
Anti Cancer

scholarly journals Polymeric micelles from poly(ethylene glycol)–poly(amino acid) block copolymer for drug and gene delivery

2009 ◽  
Vol 6 (suppl_3) ◽  
Author(s):  
Kensuke Osada ◽  
R. James Christie ◽  
Kazunori Kataoka
Keyword(s):  
Gene Delivery ◽  
Polymeric Micelles ◽  
Genetic Diseases ◽  
Cancer Drug ◽  
Biological Research ◽  
Medical Treatments ◽  
Technical Problems ◽  
Anti Cancer ◽  
Poly Ethylene ◽  
Drug And Gene Delivery

Dramatic advances in biological research have revealed the mechanisms underlying many diseases at the molecular level. However, conventional techniques may be inadequate for direct application of this new knowledge to medical treatments. Nanobiotechnology, which integrates biology with the rapidly growing field of nanotechnology, has great potential to overcome many technical problems and lead to the development of effective therapies. The use of nanobiotechnology in drug delivery systems (DDS) is attractive for advanced treatment of conditions such as cancer and genetic diseases. In this review paper for a special issue on biomaterial research in Japan, we discuss the development of DDS based on polymeric micelles mainly in our group for anti-cancer drug and gene delivery, and also address our challenges associated with developing polymeric micelles as super-functionalized nanodevices with intelligent performance.

Screening of 129 FDA approved anti-cancer drugs in colorectal cancer cell lines resistant to oxaliplatin or irinotecan (SN38).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Jan Stenvang ◽  
Christine Hjorth Andreassen ◽  
Nils Brünner
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cell Viability ◽  
Cell Line ◽  
Cell Lines ◽  
Resistant Cell ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Drug Candidates ◽  
Anti Cancer

642 Background: In metastatic colorectal cancer (mCRC) only 3 cytotoxic drugs (oxaliplatin, irinotecan and fluorouracil (5-FU)) are approved and the first and second line response rates are about 50% and 10-15%, respectively. Thus, new treatment options are needed. Novel anti-cancer drug candidates are primarily tested in an environment of drug resistance and the majority of novel drug candidates fail during clinical development. Therefore, “repurposing” of drugs has emerged as a promising strategy to apply established drugs in novel indications. The aim of this project was to screen established anti-cancer drugs to identify candidates for testing in mCRC patients relapsing on standard therapy. Methods: We applied 3 parental (drug sensitive) CRC cell lines (HCT116, HT29 and LoVo) and for each cell line also an oxaliplatin and irinotecan (SN38) resistant cell line. We obtained 129 FDA approved anti-cancer drugs from the Developmental Therapeutics Program (DTP) at the National Cancer Institute (NCI) ( https://dtp.cancer.gov/ ). The parental HT29 cell line and the drug resistant sublines HT29-SN38 and HT29-OXPT were exposed to 3 concentrations of each of the anti-cancer drugs. The effect on cell viability was analyzed by MTT assays. Nine of the drugs were analyzed for effect in the LoVo and HCT116 and the SN38- and oxaliplatin-resistant derived cell lines. Results: None of the drugs caused evident differential response between the resistant and sensitive cells or between the SN38 and oxaliplatin resistant cells. The screening confirmed the resistance as the cells displayed resistance to drugs in the same class as the one they were made resistant to. Of the drugs, 45 decreased cell viability in the HT29 parental and oxaliplatin- or SN-38 resistant cell lines. Nine drugs were tested in all nine CRC cell lines and eight decrease cell viability in the nine cell lines. These included drugs in different classes such as epigenetic drugs, antibiotics, mitotic inhibitors and targeted therapies. Conclusions: This study revealed several possible new “repurposing” drugs for CRC therapy, by showing that 45 FDA-approved anti-cancer drugs decrease cell viability in CRC cell lines with acquired drug resistance.

scholarly journals Inventions and Innovations in Preclinical Platforms for Cancer Research

2018 ◽  
Author(s):  
Khashayar Moshksayan ◽  
Navid Kashaninejad ◽  
Mohammad Said Saidi
Keyword(s):  
Cell Culture ◽  
Animal Studies ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Spheroid Formation ◽  
Multicellular Spheroids ◽  
Cell Culture Systems ◽  
Anti Cancer ◽  
Size Uniformity

Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumor models. The complex tumor microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.

scholarly journals PFKFB3 Inhibition Attenuates Oxaliplatin-Induced Autophagy and Enhances Its Cytotoxicity in Colon Cancer Cells

2019 ◽  
Vol 20 (21) ◽  
pp. 5415 ◽  
Author(s):  
Siyuan Yan ◽  
Nan Zhou ◽  
Deru Zhang ◽  
Kaile Zhang ◽  
Wenao Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Viability ◽  
Cancer Cells ◽  
Glycolytic Enzyme ◽  
Cancer Drug ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
And Migration

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), a glycolytic enzyme highly expressed in cancer cells, has been reported to participate in regulating metabolism, angiogenesis, and autophagy. Although anti-cancer drug oxaliplatin (Oxa) effectively inhibits cell proliferation and induces apoptosis, the growing resistance and side-effects make it urgent to improve the therapeutic strategy of Oxa. Although Oxa induces the autophagy process, the role of PFKFB3 in this process remains unknown. In addition, whether PFKFB3 affects the cytotoxicity of Oxa has not been investigated. Here, we show that Oxa-inhibited cell proliferation and migration concomitant with the induction of apoptosis and autophagy in SW480 cells. Both inhibition of autophagy by small molecule inhibitors and siRNA modification decreased the cell viability loss and apoptosis induced by Oxa. Utilizing quantitative PCR and immunoblotting, we observed that Oxa increased PFKFB3 expression in a time- and dose-dependent manner. Meanwhile, suppression of PFKFB3 attenuated both the basal and Oxa-induced autophagy, by monitoring the autophagic flux and phosphorylated-Ulk1, which play essential roles in autophagy initiation. Moreover, PFKFB3 inhibition further inhibited the cell proliferation/migration, and cell viability decreased by Oxa. Collectively, the presented data demonstrated that PFKFB3 inhibition attenuated Oxa-induced autophagy and enhanced its cytotoxicity in colorectal cancer cells.

Studies with plant cell cultures of Catharanthusroseus. Oxidative coupling of dibenzylbutanolides catalyzed by plant cell culture extracts

1992 ◽  
Vol 70 (7) ◽  
pp. 2115-2133 ◽  
Author(s):  
James P. Kutney ◽  
G. M. Hewitt ◽  
Terence C. Jarvis ◽  
Jan Palaty ◽  
Steven J. Rettig
Keyword(s):  
Cell Culture ◽  
Plant Cell ◽  
Cell Cultures ◽  
Oxidative Coupling ◽  
Plant Cell Culture ◽  
Plant Cell Cultures ◽  
Cancer Drug ◽  
Synthetic Route ◽  
Anti Cancer ◽  
Commercially Important

Utilizing appropriate dibenzylbutanolides, for example 7, obtained via an efficient synthetic route from readily available aldehydes, and cell-free extracts obtained from Catharanthusroseus cell cultures, it was possible to achieve enzyme-catalyzed oxidative coupling of 7 to picropodophyllotoxin analogues. Studies are presently underway to convert such compounds to intermediates employed in the synthesis of the commercially important anti-cancer drug, etoposide.

Microdfluidic Based 3-Dimensional Cell Culture Platform

2008 ◽  
Author(s):  
Song-Bin Huang ◽  
Min-Hsien Wu ◽  
Zhanfeng Cui ◽  
Zheng Cui ◽  
Gwo-Bin Lee
Keyword(s):  
Cell Culture ◽  
Drug Testing ◽  
Research Work ◽  
Three Dimensional ◽  
Cancer Drug ◽  
Pulsation Frequency ◽  
3 Dimensional ◽  
Anti Cancer ◽  
D Cell ◽  
One Step

This study reports a new perfusion-based, micro three-dimensional (3-D) cell culture platform for drug testing using enabling microfluidic technologies. In this work, a perfusion-based, micro 3-D cell culture platform is designed and is fabricated based on SU-8 lithography and polydimethylsiloxane (PDMS) replication processes. One of the key features of the system is that the incorporation of a multiple medium pumping mechanism, consisting of 15 membrane-based pneumatic micropumps with serpentine-shape (S-shape) layout, coupled with a pneumatic tank, into the micro 3-D cell culture platform to provide efficient and economical culture medium delivery. Moreover, a “smart cell/agarose (scaffold) loading mechanism” was proposed, allowing the cell/3-D scaffold loading process in one step and avoiding too much laborious works and manual error. The results show that in all of the 15 S-shape pneumatic micropumps studied, the medium delivery mechanism is able to provide a uniform flow output ranging from 5.5 to 131 μl/hr depending on the applied pulsation frequency of the micropumps. In addition, the cell/agarose (scaffold) loading mechanism was proved to be able to perform sample loading tasks precisely and accurately in all of the 15 microbioreactors integrated. Furthermore, anti-cancer drug testing was successfully demonstrated using the proposed culture platform and fluorescent microscopic observation. As a whole, because of miniaturization, not only does this perfusion 3-D cell culture platform provide a homogenous and steady cell culture environment, but it also reduces the need for human intervention. Moreover, due to the integrated pumping of the medium and the cell/agarose (scaffold) loading mechanisms, time efficient and economical research work can be achieved. These characteristics are found particularly useful for high-precision and high-throughput 3-D cell culture-based drug testing.

scholarly journals Agarose multi-wells for tumour spheroid formation and anti-cancer drug test

2016 ◽  
Vol 158 ◽  
pp. 41-45 ◽  
Author(s):  
Yadong Tang ◽  
Jianmiao Liu ◽  
Yong Chen
Keyword(s):  
Cancer Drug ◽  
Spheroid Formation ◽  
Tumour Spheroid ◽  
Drug Test ◽  
Anti Cancer
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