scholarly journals Generation of a co-culture cell micropattern model to simulate lung cancer bone metastasis for anti-cancer drug evaluation

RSC Advances ◽  
2017 ◽  
Vol 7 (35) ◽  
pp. 21837-21847 ◽  
Author(s):  
Huixiang Zhong ◽  
Liuyang Xuan ◽  
Dandan Wang ◽  
Jianhua Zhou ◽  
Yan Li ◽  
...  

A549/OB co-culture micropattern was fabricated through μ-eraser strategy to mimic lung cancer bone metastasis for DOX efficacy evaluation.

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 624
Author(s):  
Qiang Liu ◽  
Tian Zhao ◽  
Xianning Wang ◽  
Zhongyao Chen ◽  
Yawei Hu ◽  
...  

Three-dimensional cultured patient-derived cancer organoids (PDOs) represent a powerful tool for anti-cancer drug development due to their similarity to the in vivo tumor tissues. However, the culture and manipulation of PDOs is more difficult than 2D cultured cell lines due to the presence of the culture matrix and the 3D feature of the organoids. In our other study, we established a method for lung cancer organoid (LCO)-based drug sensitivity tests on the superhydrophobic microwell array chip (SMAR-chip). Here, we describe a novel in situ cryopreservation technology on the SMAR-chip to preserve the viability of the organoids for future drug sensitivity tests. We compared two cryopreservation approaches (slow freezing and vitrification) and demonstrated that vitrification performed better at preserving the viability of LCOs. Next, we developed a simple procedure for in situ cryopreservation and thawing of the LCOs on the SMAR-chip. We proved that the on-chip cryopreserved organoids can be recovered successfully and, more importantly, showing similar responses to anti-cancer drugs as the unfrozen controls. This in situ vitrification technology eliminated the harvesting and centrifugation steps in conventional cryopreservation, making the whole freeze–thaw process easier to perform and the preserved LCOs ready to be used for the subsequent drug sensitivity test.


2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Tae Woo Kim ◽  
Da-Won Hong ◽  
Sung Hee Hong

Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) is a well-known therapeutic target for type 2 diabetes as well as is a potential target for effective anti-cancer drug, since PPARγ ligands such as ciglitazone (Cig) frequently cause cell death in many types of cancer cells and suppress tumor growth. However, many cancer patients acquire chemo-resistance or radio-resistance after chemo or radiotherapy, and it is still unclear. In the difficulty of well-known anti-cancer drugs, we developed a novel PPARγ agonist CB13 (1-benzyl-5-(4-methylphenyl) pyrido [2,3-d]pyrimidine-2,4(1H,3H)-dione) and investigated the anti-cancer effect and cell death mechanism on human non-small cell lung cancer (NSCLC) cells. With anti-cancer effect of Cig, CB13 also causes inhibition of cell growth by decreasing cell viability, increasing the release of LDH, and increasing caspase-3, and caspase-9 activities. CB13 generates reactive oxygen species (ROS) and causes cell death via ER stress in NSCLC and radio-resistant NSCLC cells (A549R and H460R), and a combination of CB13 and radiation induces greater ER stress and cell death when compared to CB13 alone. Taken together, our results suggest that a combination of CB13 and radiation may overcome radio-resistance caused by radiotherapy.


2021 ◽  
Vol 28 ◽  
Author(s):  
Minnatallah Al-Yozbaki ◽  
Peter J. Wilkin ◽  
Girish Kumar Gupta ◽  
Cornelia M. Wilson

: Lung cancer is a leading cause of cancer deaths worldwide. The management of lung cancer treatment is often ineffective as a result of the development of drug resistance, reactions to treatment, drug-drug interactions or non-specific targeting of the anti-cancer drugs. Natural compounds show promise and potential activity in lung cancer with very few side effects. While, the combinatorial action of an anti-cancer drug with a natural compound provide synergistic action which help to boost the overall therapeutic action against cancer cells. In cancer, there is a dysregulation of apoptosis which facilitates the cancer cell to survive resulting in progression of the cancer. Many cancer drugs cause mutations of genes that regulate the cancer which should kill the cancer cell but lead to chemoresistance. There are many natural compounds that could specifically target different cell signalling pathways associated with cancer progression to provide a cytotoxic effect in the target cell. The importance of these compounds is emerging in many therapies developed with dual action often including a natural compound. In this review, we present a selection of these natural compounds and how they target lung cancer cells with a focus on the cell signalling pathways. Further work is required to delineate the potential action of natural compounds in the treatment against cancer.


2016 ◽  
Vol 7 (2) ◽  
pp. 741-751 ◽  
Author(s):  
Swee-Ling Lim ◽  
Yong-Meng Goh ◽  
M. Mustapha Noordin ◽  
Heshu S. Rahman ◽  
Hemn H. Othman ◽  
...  

In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20054-e20054
Author(s):  
Nariyasu Nakashima ◽  
Dage Liu ◽  
Takayuki Nakano ◽  
Yusuke Kita ◽  
Xia Zhang ◽  
...  

e20054 Background: Ribonucleotide reductase M1 (RRM1) is involved in regulation of cell proliferation and synthesis of deoxyribonucleotides for DNA. It is also a cellular target for gemcitabine (GEM) and overexpression of RRM1 was reported to be associated with the resistance to GEM. Though RRM1 expression has been reported as the biomarkers in predicting the response to chemotherapy clinically, the value of GEM remains inconsistent and controversial. Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is a newly developed in vitro chemosensitivity test that could directly inspect the anti-cancer drug sensitivity with fresh tumor tissue. With use of CD-DST test, we have verified the predictive value of RRM1 expression to the anti-cancer agent sensitivity for GEM in non-small cell lung cancer (NSCLC) tumor. Here, the predictive value of biomarker RRM1 to GEM was further verified with CD-DST. Methods: Twenty-five patients with primary NSCLC were used in this study. Expression of RRM1 was assessed by immunohistochemistry. For CD-DST test, viable cells were collected from fresh surgical specimen and embed into the collagen gel droplets in 3D condition. Tumor cells were exposed to GEM for 1 hour and further incubated with serum-free culture medium for 7 days. The in vitro sensitivity was expressed as the percentage T/C ratio, where T was the total volume of the treated group and C was the total volume of the control group. Results: 1)Anti-cancer drug sensitivity: The sensitivity for GEM (T/C%) was 76.2 ± 30.5. 2)Expression of biomarkers: RRM1 expression was 39.2 ± 28.2 %. 3) Correlation: The expression of RRM1 significantly correlated with drug sensitivity for GEM (r = 0.446, p = 0.0256). Higher expression of RRM1 indicated worse anti-cancer drug sensitivity for GEM. Conclusions: The significant correlation between the RRM1 expression and sensitivity to GEM was proved with CD-DST in NSCLC tumors. The expression of RRM1 may become a useful biomarker in predicting the drug sensitivity for GEM in NSCLC.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3930
Author(s):  
Sangun Park ◽  
Tae Kim ◽  
Soo Kim ◽  
Seungkwon You ◽  
Youngmee Jung

Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.


Sign in / Sign up

Export Citation Format

Share Document